THE RETINA
DR.
AMER ISMAIL ABU IMARA
JORDANIAN BOARD OF OPHTHALMOLOGY
INTERNATIONAL COUNCILOF OPHTHALMOLOGY
PALESTINIAN BOARD OF OPHTHALMOLOGY
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Development of the retina
The eye is externalized portion of the brain .
Formation of the eye begins with lateral
outpouchings of the forebrain during the third
week of development .
The development of the optic cup ( optic vesicle
) reaches a stage where the outer layer of the
optic vesicle becomes the retinal pigment
epithelium , while the inner layer of the optic
vesicle becomes the multilayered neurosensory
retina . anterior extension of both layers become
the double layer ciliary epithelium .
The ocular ventricle is the potential space
between the retinal pigment epithelium and the
neurosensory retina.
PIGMENT EPITHELIUM
 Is homolog of the epithelium of the choroid
plexus of the brain .
 The retinal pigment epithelial cells acquire
during development tight junctions that
form a barrier between the neurosensory
retina and the choriocapillaries .
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CELLULAR ORGANIZATION OF THE RETINA
The layers of cell nuclei are as follows :
the outer nuclear layer (ONL) , which contains
the cell bodies of the photoreceptors.
The inner nuclear layer (INL) , which contains
the cell bodies of horizontal neurons , bipolar
neurons , amacrine neurons , displaced ganglion
cells and those of the glial cells of Muller .
The ganglion cell layer , which contains the cell
bodies of most of the ganglion cells , displaced
amacrine cells and those of the astroglial cells .
Between the ONL and the INL is the outer
plexiform layer (OPL)
 OPL = synapses of the photoreceptors
,bipolar cells and horizontal cells .
 Between the INL and the ganglion cell
layer is the inner plexiform layer ( IPL)
 IPL= synapses of the bipolar cells ,
amacrine cells and ganglion cells .
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The optic fibers consist of the axons of the
ganglion cells and are unmyelinated while
within the retina . these fibers leave the
retina at the optic disc going out of the
globe posteriorly as the optic nerve .
 In the retina Muller cell processes fill in
almost all volumes not occupied by nerve
cells , relatively rare astroglia or blood
vessels .
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There appear no physical barrier to
diffusion of molecules of moderate size
from the vitreous through the retina into
the ocular ventricle .
 There is no hindrance to electrical current .
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BLOOD SUPPLY OF THE RETINA
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Blood vessels coming from the optic nerve
head supply the inner two thirds of the
retina . the outer one third is supplied by
the choroid .
 The inner blood –retinal barrier is formed
by tight junctions between retinal blood
vessels endothelial cells .
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RETINAL NEUROANATOMY AND ITS
PHYSIOLOGIC SIGNIFICANCE
The input to the retina is a time-varying twodimensional display of an image in its focal
plane .
The image consists of patches of illumination
varying in shape, intensity and spectral content .
the information input is received by the
PHOTORECEPTORS . the output of the
photoreceptors is processed by a variety of
subsequent retinal neurons and finally by the
retinal ganglion cells whose axons leave the
retina for higher brain centers .
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The information leaving the retina via
axons of the ganglion cells represents a
small number of information processing
streams parceling certain types of
information contained in the visual input to
axons with particular routing . the axons of
the ganglion cells have several principal
as well as minor destinations, and the cells
are sometimes classified by their axonal
targets .
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The retina also has outputs to the outermost
layers of the superior colliculus , where the
information directly or indirectly interacts with
motor pathways influencing the extraocular
muscles ,visually concerned cerebellar
pathways , such as those dealing with head and
neck movements , and with vestibular and
auditory centers .
Pretectal region indirectly receives retinal
information important for parasympathetic and
sympathetic regulation of the pupil and ciliary
muscle .
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PHOTORECEPTORS
These cells are rods and cones . their cell
bodies lie in the ONL.
They synapse at the OPL.
An elongated part of the cell protrudes toward
the RPE and this part is divided to outer
segment and inner segment which are linked by
the ciliary stalk .
The ellipsoid ( the apical portion of the inner
segment ) is rich of mitochondria .
There are two types of photoreceptors : rods and
cones .
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Little is understood about how photoreceptor shape
affects function .
The outer segments of both rods and cones contain
many double membrane discs or flattened saccules .
The discs are isolated in rods , but in cones they
connects to cell membrane .
The discs are of great importance because the visual
pigments , which capture the photons to begin the visual
process , appear to be built into the discs .
The visual pigments are insoluble .
They are intrinsic membrane proteins .
They constitute > 50% of the protein of the outer
segment .
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Visual pigment = aldehyde of vit.A and various
proteins .
Outer segments are capable of regeneration .
Destruction may occur on RD , vit.A def.
Surrounding the photoreceptor outer and inner
segment a gel termed interphotoreceptor matrix
(IPM) .
Both cone and rod discs shed and are
phagocytosed by RPE.
Rods shed shortly after morning
Cones peak shedding at the end of the day.
Outer segment … production and destruction .
RECEPTOR OUTER SEGMENT AND
PIGMENT EPITHELIUM RELATIONS
 RPE is implicated in the ocular transport of
vit.A and it’s derivatives .
 The regeneration of visual pigment is one
factor in dark adaptation after the
significant bleaching of such pigment .
 The RPE contains melanosomes which
contain melanin .
 The melanosomes minimize the scattering
of light from one photoreceptor to another.
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Detachment of the retina consists of the physical
separation of the retina from its close
approximation to the RPE .
Parameters that contribute to attachment are :
factors regulating the volume of fluid in the
ocular ventricle .
acid mucopolysaccharides , known to be present
in the fluid of the ocular ventricle , which could
contribute to its viscosity or to the cohesion of
neighboring membranes .
a barb action of the elongated melanosomes in
the long microvilli from the RPE .
the RPE also has phagocytic function . the
membrane of the outer segment heals
over.
 The receptor axes are so tipped as to
orient them to the exit pupil of the eye
rather than to the center of the ocular
sphere . this maximizes the ability of any
one photoreceptor to capture light .
 During the act of accommodation
orientation of receptor outer segments is
altered .
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It is now clear that after bleaching of
photopigment , the 11-cis-retinaldehyde has
been converted to all-trans-retinaldehyde . there
is then a conversion to all-trans-retinol by a
dehydrogenase .
The RPE is the site where reoxidation of retinol
to retinal occurs , as well as reisomerization of
the all-trans-isomer to the 11-cis-isomer .
Important carrier proteins are involved in moving
these vitamin A derivatives between the
photoreceptors and RPE in both directions .
DISTRIBUTION OF PHOTORECEPTORS
AND OTHER NEURONS WITHIN THE
RETINA
 How different types of photoreceptors are
distributed in retinas .
 Regions biased for inspecting details are
richer in cones by virtue of containing
thinner cones and more of them per unit
area than elsewhere and more ganglion
cells per unit area as well . such a region
is termed central region .
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Physiologically ,central regions tend to be
free of major blood vessels and in certain
retinas even capillaries .
 In the human the extent of the cone-rich
area is about 5.5mm in diameter, and it
tends to be variably demarked by the
presence of yellow , nonphotolabile
carotenoids in photoreceptor axons and
some inner retinal cells . the pigment is
largely zeaxanthin . these pigments give
the region the name .. macula lutea .
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The center of the cone-rich region
contains a pit or fovea .
 In the human the full depression occupies
about 5 degrees of arc or about 1.5mm on
the retina .
 In the center of the fovea there is the
foveola ( 54 minutes of arc =
260micrometer ).
 Here only photoreceptor type present (
cones ).
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Cones in this region have the finest
diameters of the retinal cones ( 1.5
micrometer ) and this is the region of
highest concentration of cones in the
retina .
 Functionally the fovea is the position of the
retina to which , by turning the eye ball , a
person brings the image of what ever is of
greatest psychologic interest in the visual
field .
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Anatomically , the retina in the central
fovea consists entirely of the outer and
inner segments of the photoreceptors , the
photoreceptor cell bodies , and the
intervening glial cell processes .
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The axons of the photoreceptors , the socalled Henle fibers , are swept horizontally
and leave the foveal area . the terminals of
foveal cones , the horizontal neurons and
bipolar neurons with which they interact ,
and those amacrine cells and ganglion
cells that receive information from the
foveal cones are centrifugally and laterally
displaced so that, in the foveolar region ,
all these elements are missing , and they
are minimized elsewhere in the fovea .
The foveola is surrounded by a parafoveal
region , and this by a perifoveal region .
 They are 2.5mm and 5.5mm in diameter
respectively .
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If one imagines a vertical line passing
through the central fovea , thus separating
nasal retina from temporal retina , axons
from ganglion cells of the temporal retina
will project to the LGN and superior
colliculus on the same side of the brain as
the eye , whereas ganglion cells from the
nasal half of the retina will cross in the
optic chiasm and terminate in the LGN and
superior colliculus of the contralateral
brain .
The adult human retina has about 120
million rods and about 6-7 million cones .
 Cone density peaks in the fovea at about
199.000 cones / mm2 , and then falls off
sharply in all directions , although there is
some concentration of cones along the
horizontal meridian , particularly in the
nasal retina .
 The area for useful color vision in humans
has a diameter of 9mm centered on the
fovea .
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The rod-free center of the fovea may be
deficient in blue sensitive cones .
 The human rod density peaks in a
somewhat elliptical ring .
 The highest rod concentration ( 160.000
/mm2 ) along this configuration occurs in
the superior retina .
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It is important to realize that when light
levels are in the photopic range of cone
function , their activity tends to command
all retinal output .
 INL contains the somal regions of bipolar
neurons and also contains those of
horizontal and amacrine neurons ,
interplexiform neurons , rare displaced
ganglion cells , and the somal regions of
the glial cells of Muller .
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In this layer it is difficult to know the exact
distribution of cells across the retinal area.
 Situation for the distribution of ganglion
cells is somewhat better , because this
region belong only to ganglion cells and
displaced amacrines .
 However , there are several varieties in
ganglion cells in terms of size and
distribution of processes
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It is fair to state that the macular region in
the human retina is rich in small ganglion
cells and that, by comparison to
concentration of cones in this region , it
seems likely that there are enough small
ganglion cells to permit the consideration
that each could receive information via
intermediate cells from a rather small
population of cones .
A chain of information transmission in
which the ratio of receptors connected via
intermediates to ganglion cells approaches
1:1 is what one might idealize for a region
of high detail discrimination .
 In other retinal regions there is a high ratio
of rods to ganglion cells and , as expected
, a high sensitivity to detecting light but
poor form discrimination .
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SYNAPTIC CONNECTIONS OF THE
RETINA
 Receptor terminals are spherules or
pedicles .
 Spherules are small and round while
pedicles are large and have flat bases
facing the rest of the OPL .
 Rods end in spherules and cones in
pedicles .
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Processes of horizontal cells and bipolar
neurons are deeply invaginated in rod
spherules but only superficially
invaginated into the bases of pedicles .
 The receptor terminal is full of synaptic
vesicles .
 There is some contacts between cones
and cones and cones and rods . these
contacts helps in spread of current
between cells .
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Horizontal cells occur in the outer portion
of the INL and are neurons whose
processes are disposed in a manner
suggesting a role in the horizontal
integration of retinal activity .
 An amacrine cell is a neuron with no
morphologically definable axon . there
soma lie in the inner aspect of the INL.
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RETINAL SYNAPTIC MECHANISMS AND
PUTATIVE CHEMICAL
NEUROTRANSMITTERS
The photoreceptors have terminals rich in
synaptic vesicles and evidence strongly
indicates that the transmitter of the
photoreceptor is glutamate , an excitatory (
depolarizing ) aminoacid .
Interphotoreceptor contacts between cones , or
rods and cones , have frequently been noted
and appear to include gap junctions , indicating
the possibility of electronic interactions between
these cells .
The photoreceptors have terminals rich in
synaptic vesicles and evidence strongly
indicates that the transmitter of the
photoreceptor is glutamate , an excitatory (
depolarizing ) aminoacid .
 Interphotoreceptor contacts between
cones , or rods and cones , have
frequently been noted and appear to
include gap junctions , indicating the
possibility of electronic interactions
between these cells .
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The action of a neurotransmitter or
neuromodulator , promoting excitation or
inhibition , is both a parameter of the
nature of the agent and of the membrane
mechanisms determining the response of
a particular cell to the agent .
 For example , the action of acetylcholine
on skeletal muscle is excitatory , but its
action on cardiac muscle is inhibitory .
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Finally , when transmitter or
neuromodulator are released it is
obviously desirable to terminate their
presence by enzyme action or other
mechanisms after they have carried out
their signaling function .
 Thus the glial cells of Muller appear to
take up and metabolize glutamate .
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ELECTRICAL ACTIVITY AND
INFORMATION PROCESSING BY
RETINAL NEURONES .
 The electrical activity of individual cells
can be recorded by intracellular electrodes
and sometimes by extracellular electrodes
( animals ) .
 Each cell in the chain of nerve cells
processing visual information has its own
receptive field .
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There is a considerable overlapping of
receptive fields of cells near each other in
the retina .
 Any receptive field has sometimes distinct
regions , such as ( center ) and ( surround
).
 When a small spot of light , at an intensity
above back ground , is first positioned on
the center and then on the surround ,
opposite responses are often elicited .
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If the spot of light is expanded to stimulate
simultaneously both center and surround
diminished or absent response will be
elicited .
 Spot of darkness also has the same
response .
 The spatial dimensions of receptive field
centers are one determinant of spatial
resolution – the smaller the center the
smaller the possible spatial resolution .
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Electrodes across the eye ( see ) a summation
of the various individual cell responses.
Retina with its population of rods and cones
modifies the signals reaching ganglion cells as a
function of its adaptational state , that is to say ,
when it is dark adapted to a lower level of
illumination or when it is light adapted to a more
intense illumination .
Altering the adaptational level involves both
photochemical and electrochemical changes in
the receptors and probably at subsequent retinal
processing levels .
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ALL EVIDENCE POINTS TO A
FUNCTIONAL ORGANISATION IN THE
RETINA AND HIGHER VISUAL SYSTEM
THAT IS RELATIVISTIC AND DIRECTED
AT DISCERNING LOCAL CONTRASTS
THAT ESTABLISH BORDERS BETWEEN
AREAL ELEMENTS IN THE COMPLEX
IMAGE OF THE VISUAL FIELD , RATHER
THAN MECHANISMS FOR ASSAYING
THE ABSOLUTE LEVELS OF LIGHT IN
LOCAL AREAS .
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A retinal locus receiving an image of an
area perceived as ( black ) at a high level
of illumination may actually be receiving a
greater absolute quantity of light than a
retinal locus receiving an image of an area
perceived as ( white ) at a dim illumination
if , in the former instance , the black area
is receiving relatively much less light than
its general surround and in the later
instance , if the white area is receiving
relatively much more light than its
surround .
Moreover , the color perceived to be
present in a patch will depend on the
nature of the perceived color in its
surround .
 NEURAL NETWORK OF VISUAL
APPARATUS ARE MORE KEYED TO
DETECTING FLUCTUATIONS IN THE
RETINAL IMAGE CAUSED BY
CHANGES IN LOCAL RELATIVE
INTENSITY THAN FOR DETECTING
STEADY DISPLAYS.
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ONE SOURCE OF THIS FLUCTUATION
IS MOVEMENT OF THE IMAGE OF THE
VISUAL FIELD ON THE RETINA .
 THE LATTER FACT RAISES AN
IMPORTANT POINT REGARDING
MOVEMENTS OF THE EYE .
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More over if by some means the image of the
visual field is made to hold its position on the
retina despite eye movements , the image fades
and is no longer seen by the observer .
This explains why the shadows of the blood
vessels of the retina are not in constant view in
superimposition on the field of vision , because
by having a fixed relation to the retina and the
pathway of light , they are adapted out of the
perceived image .
The important point therefore is that a normal
fine instability of the eye contributes to the
normal visual process .
Photoreceptors hyperpolarize when
exposed to flashes of light .
 Single rod may be excited by a single
quantum of light .
 For a single rod to be excited by a single
photon represents an exquisite sensitivity .
 There is more synaptic activity in the dark .
 In the dark a current is flowing into the
outer segment from the rest of the
photoreceptor
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The effect of a flash of light is to diminish
this dark current . this diminution is
achieved largely by decreasing the
conductance for sodium ion across the
plasma membrane of the outer segment .
 Light causes a decrease rather than
increase in calcium activity in outer
segments.
 In the dark a low level of calcium ions
enters outer segments along with sodium
ions.
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This entry of calcium ions is countered by
the activity of a counterporting mechanism
that exchanges intracellular calcium and
potassium for external sodium .
 Since in the dark calcium enters the cell
along with sodium via the light modulated
channels , and as the exchange
mechanism is not regulated by light , when
the light sensitive channel is closed , the
continuing operation of the exchange
mechanism decrease intracellular calcium
.
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The main agent for regulating the
channels for entry of sodium is cyclic
guanosine monophosphate (cGMP) .
 Photoreceptors are extraordinarily rich in
cGMP.
 Light causes losses of cGMP by a
complex mechanism called the cyclic GMP
cascade , wherein bleached rhodopsin
activates a nucleotide-binding protein ,
and this intermediate activates a
cyclicGMP phosphodiesterase that
hydrolyzes cyclic GMP to GMP .
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Studies have shown that cyclic GMP can
act on the inner face of the plasma
membrane of the rod outer segment to
open conductances .
 This effect is suppressed by light .
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It is therefore clear that a channel involved
in the transduction in rods , and also in
cones , is light sensitive , because
appropriate levels of cGMP keep it open in
the dark , while the loss of cGMP through
the activation of cGMP phosphodiesterase
via the light initiated cGMP cascade allows
the channel to close .
 To complete the story , cGMP is
regenerated from GTP by the activity of
guanylate cyclase .
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Chelating calcium rapidly and massively
increased cyclic GMP levels in
photoreceptors , suggesting that this
enzyme is inhibited by calcium .
 The significance of light insensitive
mechanism exchanging calcium and
potassium for sodium is thus seen as a
way to promote the resynthesis of cGMP
by reducing the calcium level after light
has caused a loss of this cyclic nucleotide
.
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Both rods and cones hyperpolarize to light
flashes , but rods recover more slowly
than do cones from bright flashes
presented against a dark background ,
and rods have a lower absolute threshold
to flashes presented against a dark
background .
Horizontal cells only sensitive to light
intensity or luminosity are called ( L ) type ,
while those whose polarity is color
sensitive are called ( C ) type.
 Horizontal cells are often coupled by gap
junctions , and their effects often feed
back onto cones , possibly to rods , and
possibly feed forward onto bipolars .
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Bipolar neurons respond to contrast , not
simply light intensity , and these center
versus surround phenomena are also
evident at the ganglion cell level .
 In the photopic range spatial detail is best
detected by brightness contrast rather
than color contrast . the best detectors of
brightness contrast are red or green cones
, the relatively sparce blue cones less so.
 Brightness contrast is poorly detected by
rods operating in the scoptopic range .
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The likely anatomic basis for the center of
this receptive field is the population of
photoreceptors with which these bipolars
are in direct synaptic contact , whereas the
surround may represent another
population of photoreceptors by which the
bipolars are indirectly influenced via
horizontal neurons .
The visual system contains ( on ) and ( off
) pathways .
 Neurons that depolarize in response to an
increase in the intensity of light above
background in their receptive field are
termed (on ) cells , where as those that
depolarize in response to the offset or
diminution of light compared to
background are termed ( off ) cells .
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Since the light diminishes the sodium
current entering the photoreceptors , all
photoreceptors hyperpolarize in response
to increasing light and depolarize to
diminishing light and are therefore ( off )
cells .
 Bipolars that depolarize to light are ( on )
cells , whereas those that hyperpolarize to
light are ( off ) cells .
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As the latter mimic the polarization
responses of photoreceptors , the synapse
between them is said to be ( sign
conserving ) .
 Conversely , the synapse between
photoreceptors and those bipolars that
depolarize to light is termed ( sign
inverting ) .
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The two bipolar classes may function in
detecting relatively bright centers in darker
surrounds , or the converse .
 Particular amacrine cells probably serve in
abstracting particular environmental
features to permit ganglion cells to
respond to such things as movements in
particular directions or to objects of
particular sizes, orientations , shapes or
patterns .
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Ganglion cells :
 ( on ) cells
 ( off ) cells
 ( on-off ) cells
 It should be remembered that individual
ganglion cells summate the effects of
numerous impinging inputs of electronic or
chemical synapses and the location of a
synapse on a cell is also of possible
significance .
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Ganglion cells largely fall into one of two
major groups characterized by whether
their discharge pattern is sustained or
phasic .
 A ganglion cell exhibiting a sustained
discharge is not responsive to the
rearrangement of dark and bright elements
in its receptive field provided that the net
illumination is constant , whereas phasic
ganglion. cells would respond to each
such change .
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Fast-conducting axons from the retina
tend to end in the magnocellular layers of
the LGN , whereas axons of medium
conduction velocity project to the
parvocellular layers of the LGN .
 Receptive fields of the ganglion cells tend
to increase with distance from the central
area or fovea .
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It should be clear from the preceding
discussion that the retina is organized to
permit the lateral interaction of nerve cell
networks and that this often can take the
form of lateral inhibition .
To summarize the foregoing discussion ,
one can consider the retina ( and higher
visual system ) to have parallel
depolarizing ( on- center ) and
hyperpolarizing ( off-center ) informational
pathways , with a neuron assigned to a
pathway by the polarity of its response to
the onset of light on its receptive field .
 Opposite effects occur with light offset ,
and cells that exhibit ( on-off ) behavior are
thought to connect to both information
streams .
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ROLE OF GLIA
 The membrane potential of the Muller cell
may reflect its behavior as a potassium
electrode .
 Glia undoubtedly have phagocytic
functions in pathologic states and certainly
functions that are still unknown .
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THE OPTIC NERVE
The optic nerve can be considered to have
four portions :
- the intraocular portion .
- intraorbital portion
- intracanalicular portion
- intracranial portion
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1 million axons that pass from each eye
into the optic nerve conduct partially
processed visual information from the
retinal ganglion cells to the lateral
geniculate body, superior colliculus ,
hypothalamus , and certain midbrain
centers .
 There are now considered to be two
parallel pathways in the anterior visual
pathways carrying different types of visual
information .
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The luminance pathway , also called M (
for magnocellular ) , utilizes larger retinal
ganglion cells with larger diameter axons
that synapse in the magnocellular layers of
the lateral geniculate body .
 They are most sensitive to change in
luminance at low light levels , subserve
motion perception , and are relatively
insensitive to color .
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Only a small proportion of all ganglion
cells are part of the M pathway .
 The color or P ( for parvocellular ) pathway
consists of smaller ganglion cells that
project to the parvocellular lateral
geniculate layers and preferentially carry
information on color and fine detail .
 This group includes the majority of retinal
ganglion cells , including the midget cells
of the foveal area .
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After passing through the lamina cribrosa to
enter the intraorbital portion , the fibers gain a
myelin sheath .
From this point onward the impulse is carried by
saltatory conduction typical of white matter tracts
and myelinated peripheral nerves .
Depolarization occurs only at the nodes of
Ranvier , with the impulse jumping from node to
node .with this saltatory conduction , the impulse
passes along the axon more rapidly than it
would by conduction of an action potential , such
as in unmyelinated fiber .
Saltatory conduction also conserves
metabolic energy , because only the
exposed portion of the axon membrane at
the node needs to be repolarized , not the
entire length of the axon .
 What will happen in demyelinating
diseases ??
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The number of fibers appear to be related
to the size of the optic disc as it is seen
clinically . the larger the optic disc , the
more the number of fibers .
 There are more than twice the number of
axons in a fetal primate eye than in the
adult eye .
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It is believed that ganglion cells die if their axons
do not successfully synapse with appropriate
targets in the brain .
After birth , this attrition of the optic nerve fibers
slows dramatically .
During a 75-year human life , the further loss of
ganglion cells , presumably from aging ,
encompasses only 25% of the total .
Blacks have larger discs and hence larger cups .
The movement along axons seems to occur by
at least two different processes : rapid axonal
transport and slow axoplasmic flow .
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Rapid axonal transport is bidirectional ,
orthograde from the ganglion cell body to the
axon terminal and retrograde from the terminal
to the ganglion cell body .
This active transport requires metabolic energy ,
which is obtained from ATP produced locally
within each axon segment along the way .
200 – 400 mm / day
A variety of chemical messages , hormones and
foreign material such as toxins and viruses can
be passengers in this system .

Slow axonal flow can be traced as the
movement of soluble proteins synthesized
in the cell body toward the axon terminal
at a rate of only 1 to 3 mm / day .
THE GLIA
 The predominant glial element in the optic
nerve head is the astrocyte .
 Their function to support the bundles of
nerve fibers as they turn to enter the optic
nerve from the retina
 Astrocytes also provide a cohesiveness to
neural compartment .

Astroglia in the nerve head presumably
also serve to moderate conditions for
neural function , for example , by
absorbing excess extracellular potassium
ions released by depolarizing axons and
by storing glycogen for use during
transient oligemia .
 They function in the nerve head like the
Muller cells of the retina .
 The oligodendrocytes form and maintain
the myelin sheaths , as they do elsewhere
in the CNS .

THE BLOOD VESSELS
 The optic nerve microvascular bed
resembles anatomically the retinal and
CNS vessels .
 The optic nerve vessels share with those
of the retina ( and of the CNS in general
)the physiologic properties of
autoregulation and the presence of the
blood brain barrier .
 Because of autoregulation , the rate of
blood flow in the optic nerve is not much
affected by intraocular pressure ( IOP ) .

In the retina and optic nerve , as in the
brain , the vascular tone is increased by
autoregulation when blood pressure rises
, increasing the resistance to flow , so that
the flow level is not affected by the
elevated blood pressure .
 Elevated IOP compresses the vein ,
increasing the total resistance to flow
through the arteriovenous circuit , which
would reduce the blood flow for a given of
arterial blood pressure .

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
However , autoregulation compensates for
venous compression by reducing the vascular
tone in other parts of the circuit as IOP rises , so
that blood flow is maintained despite the venous
compression caused by intraocular pressure .
Autoregulation seems to be accomplished in
part as a response to the degree of arterial
stretching and in part as metabolic
autoregulation … as carbon dioxide
concentration , pH , or oxygen level .
CO2 is a particularly powerful vasodilator . CO2
accumulates because of inadequate blood flow ,
the vessels dilate and the blood flow increases .
PAPILLEDEMA ( OPTIC NERVE-HEAD
SWELLING )
 A variety of intracranial conditions may
result in papilledema .
 Obstruction of cerebrospinal fluid exit ,
which results in an elevated intracranial (
hydrostatic pressure .
 Subarachnoid space extends through the
optic canal around the optic nerve and the
hydrostatic pressure is transmittied there
around the optic nerve .




The central retinal vein , as it crosses the nerve
sheaths in the mid-orbit is subject to external
compression by the subarachnoid pressure .
When the subarachnoid pressure exceeds
venous pressure , compression of the vein
increases resistance to flow at that point and
elevates slightly the venous pressure upstream .
If spontaneous venous pulsations are present in
the optic disc , as happens in many normal
individuals , they disappear when the elevated
central retinal venous pressure exceeds the
normal IOP .
It is now thought that the main
pathophysiologic event is an impairment of
slow axoplasmic flow . the tissue pressure
of the axons within the eyes is equal to
IOP , whereas in the orbit the intra-axonal
tissue pressure is governed by the
subarachnoid pressure .
 the lamina cribrosa is the partition that
separates the two pressure compartments
, where axons are subjected to this
pressure gradient .

under normal conditions the IOP is greater
than the subarachnoid pressure and the
gradient may be thought of as augmenting
the movement of axoplasm out of the eye .
 however , when intracranial pressure
equals or exceeds IOP , the forces of slow
axoplasmic flow encounter a diminished or
reverse pressure gradient . the axons in
the optic nerve head become distended .

although slow axoplasmic flow is impaired
, the axons often continue to function .
 visual function may be quite normal in
chronic papilledema for a long time ,
except that the physiologic blind spot is
enlarged when the swollen disc displaces
the inner retina next to the optic nerve
head .

Not all swellings of the optic nerve head
are papilledema due to increased
subarachnoid pressure .
 For example : anterior ischemic optic
neuropathy in which the nerve head swells
is most likely an infarction of the anterior
optic nerve .
 Other swellings may occur as a result of
neoplastic infiltration , acute glaucoma ,
and hereditary neuropathy .

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
OPTIC ATROPHY
Nonglaucomatous optic atrophy is characterized
by a loss of axons ( and their retinal ganglion
cells ) in response to lethal insult to the cell .
With loss of its substance , the optic disc flattens
and turns pale .
Localized insults , which occur most often in the
anterior optic nerve and retina , injure bundles of
axons and in the visual field produce scotomas
and other visual field defects that are shaped
like the course of nerve fiber bundles .

Lesions of the posterior optic nerve also
can rarely injure bundles of axons and
produce nerve fiber bundle defects . the
usual compressive lesion in this location
almost always has a diffuse effect or
affects preferentially the small diameter
macular fibers , resulting in a central
scotoma .
Whichever the underlying etiology of optic
atrophy , the integrity of the axon is
interrupted anatomically or physiologically
at some point in its course .
 The proximal segment of the axon , being
disconnected from its ganglion cell ,
promptly degenerates . it is no longer
receives support through the orthograde
axonal transport mechanism .

There remain the ganglion cell and the
attached fragment of axon that extends
from the ganglion cell to the cite of injury .
 It has been shown that mammalian optic
nerve fibers cannot only regenerate , but
reestablish connections with their target
sites in the central nervous system if
provided with a segment of peripheral
nerve tissue as a bridge within which to
grow .

When atrophy occurs , the astroglia
migrate into the spaces vacated by the
degenerated axons . blood vessels are
reduced in number but remain in
proportion to the glial and neuronal tissue
that persists and requires nutrition .
 When optic atrophy occurs , the typically
red color of the optic disc rim becomes
pale .

COLOR VISION
 Color is purely a sensory phenomenon
and not a physical attribute .
 Human awareness of color arises out of
subjective visual experiences in which
given sensations are ascribed names .
 Agreement between individuals in color
naming derives from a tacit acceptance
that given sensations can be reliably
described with color names .

The perception of color varies complexly
as a function of multiple parameters ,
including the spectral composition of light
coming from the object , the spectral
composition of light emanating from
surrounding objects , and the state of light
adaptation in the subject just prior to
viewing any given object .
 A remarkable and as yet not completely
understood phenomenon that is
characteristic of color vision is that of color
constancy .


Color constancy refers to the phenomenon
in which the apparent color of an object
does not seem to vary appreciably when
the wavelengths and intensity of light
illuminating the object are altered .
Color constancy appears to be related to a
phenomenon in which :
 colors acquire their appearance primarily
by relative comparisons to other objects in
their immediate vicinity and
 these comparisons change only minimally
with broad changes in spectral mixtures of
light falling on scenes .

COLOR AND VISIBLE SPECTRUM
 The rainbow of hues visible in the solar
spectrum was first reported by Sir Issac
Newton , who correctly supposed that
individual components of the spectral
mixture were in some way related to
differential stimulation of photoreceptor
units in the eye , providing the basis for
the physical stimulus evoking color
sensation .

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
If a prism is placed in the path of a narrow beam
of sunlight , the path of the light beam will be
refracted or bent toward the base of the prism .
Short wavelengths are bent to a greater extent
than are long wavelengths.
The index of refraction for an optical medium
differs according to wavelength .
This variable extent of refraction spreads a
polychromatic white beam of light into its
component wavelengths , a phenomenon
referred to as spectral dispersion .
The array of individual wavelengths thus
exposed is referred to as the visible spectrum .




The sensations that these individual
wavelengths evoke are called the spectral
colors.
Violet light at a wavelength of 430 nm, blue light
of 460nm , green light of 520nm , yellow light of
approximately 575nm, orange light of 600nm ,
and red light of 650nm.
Wavelengths falling between these values
produce color sensations that are often given
compound names , such as blue-green or
yellow – green .
Remember , though, that such stimuli remain
monochromatic , and the sensations they evoke
depend on much more than just wavelength and
intensity .
The color a given stimulus evokes
depends critically on the context within
which it is seen, a phenomenon called
simultaneous color contrast .
 As will be shown later , color is neural
encoded in the afferent visual system by
cells whose receptive fields are tuned to
the detection of simultaneous color
contrasts .

THE TRICHROMATIC THEORY OF
HUMAN COLOR VISION
 Two major theories to explain the
properties of human color vision .
 These two principal theories are now
referred to as the theory of trichromacy (
or the Young-Helmholtz-Maxwell theory )
and the opponent process theory .



Over the past several decades , it has become
apparent that human and nonhuman primate
color vision is indeed mediated by an essentially
trichromatic process at the receptor level , but is
encoded for neural transmission in a physiologic
paradigm of the color opponent process .
Studies of individual photoreceptors , allowed
the identification of three mutually exclusive
classes of cones in the primate retina having
differing , but overlapping , spectral sensitivities .



One class of photoreceptors has a spectral
sensitivity that peaks at approximately 440nm to
450nm . these receptors , which are more
sensitive to the short wavelength end of the
spectrum , are sometimes referred to as short
wavelength sensitive receptors , or blue cones .
A second class of middle wavelength sensitive
receptors has a spectral sensitivity that peaks at
between 535and 550 nm , sometimes referred to
as green cones .
The third class has a spectral sensitivity peaking
at between 570 and 590 nm . these are referred
to as long wavelength sensitive photoreceptors
or red cones .

The overlapping of the spectral
sensitivities of these three classes of
cones means that no individual class of
cones can be stimulated in isolation by
any one wavelength .





THE OPPONENT COLOR THEORY
Certain select pairs of colors such as red versus
green or yellow versus blue were found to be
mutually exclusive .
Mixing lights of such colors did not yield
composite sensations .
For instance , red light and green light mixed
together produced an appearance of yellow ,
while mixing blue light with yellow light produced
an appearance of white .
Thus some colors seems to be mutually
exclusive or opponents of one another .
COLOR MIXING , METAMETRIC
MATCHES , AND COMPLEMENTARY
WAVELENGTHS .
 Helmholtz found that any colored light one
wished to use as a reference could be
matched by a suitable mixture of three
strategically chosen lights mixed together .
 While Helmholtz established the
qualitative nature of this relationship , it
was later put on a quantitative basis by
Maxwell .

Mixtures of light that produce identicalappearing colors are called metameric
matches .
 Mixtures that are physically identical to
one another ( have identical spectral
compositions ) are said to be isomeric
matches .
 Normal observers can always produce
metameric matches , but only if at least
three spectral lights are given.

While such metameric matches can be
physically very different from one another (
in terms of their spectral distributions ) ,
they nonetheless appear to be identical in
color and brightness .
 This appearance of sameness is linked to
the relative extent to which each of the
three retinal cone classes are excited .

Light mixtures that cause the same
proportional stimulation of the three
receptors will result in the same sensation
.
 In those special cases of metameric
matches of light seen as “ white “ , it is
often possible to achieve a match by the
proper mixing of only two appropriately
chosen spectral lights .
 Such pairs of monochromatic light sources
are said to have complementary
wavelengths .


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

NEURAL ENCODING OF COLOR
The receptive fields of neurons are classified as
being color coded , if some aspect of the cell
responses are found to be specific for some
color attribute .
For instance , a cell may respond more
vigorously to stimulation by light of one
wavelength than of another , or the nature of the
response may differ as a function of wavelength
.
Two broadest categories of such cells in the
anterior visual system are opponent color cells
and double opponent cells .
OPPONENT COLOR CELLS
 Tracing afferent visual pathways beyond
the photoreceptors , the first cells found to
have specific color-related properties are
the opponent color cells .
 Such cells have differing polarity of
responses for differing portions of the
visible spectrum .


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

An example of an opponent color cell is as
follows :
Stimulation by yellow light increases the tonic
firing rate of such a cell , whereas stimulation by
blue light inhibits or eliminates its rate of firing .
Stimulation by similar-sized spots of white light
produces no response .
The latter phenomenon may be explained by
presuming that simultaneous white stimulation of
both excitatory and inhibitory components of the
cell’s receptive field will result in a net zero
response in firing rate .
Opponency of such cells can be
characteristically divided into two large
groups : those having blue-yellow
opponency , and those having red-green
opponency .
 Red-green color opponent cells are tuned
to detection of varying levels of stimulation
of middle and long wavelength sensitive
cones , and are best suited to the
detection of red-green color contrasting
borders .

It is believed that there are also cells that
sum the input of red and green cones to
produce a yellow signal .
 Blue – yellow opponent cells then detect
levels of stimulation of blue cones as
compared to the summed effect of
stimulating both red and green cones .

DOUBLE OPPONENT CELLS
 Cells that have opponent receptive field
properties for both color and space are
said to be double opponent .
 Double opponent cells are optimally
organized for the detection of
simultaneous color contrast .
 The phenomenon of simultaneous color
contrast can be demonstrated by viewing
restricted areas surrounded by contrasting
color regions .

For instance , a small field of gray
surrounded by a field of red will appear to
contain a greenish cast .
 Conversely , the same gray spot viewed in
any region surrounded by green will
acquire a reddish appearance .
 The general rule of simultaneous color
contrast is that the color of a restricted
region will tend toward the complementary
color of its surround .

Simultaneous color contrast is closely
related to the phenomenon of color
constancy referred to previously .
 The color that a given light will appear to
have depends critically upon closely
adjacent areas with which it is compared
and contrasted .
 A localized area illuminated by
monochromatic light of 585nm wavelength
can take on a variety of seemingly
different colors , depending entirely on the
areas surrounding it .




For instance , a spot of 585nm will acquire a
green color when embedded in a surround of
650nm but will appear to be red when
surrounded by a field of 540 nm .
When surrounded by a field of identical
wavelength but 0.7 log unit brighter , it will
acquire a gray appearance , whereas if the
surround of the same wavelength is 2 log units
brighter , the spot will appear to be black .
Again , if the spot of 585nm light is surrounded
by a field of somewhat shorter wavelength , for
instance 570nm , but 1 log unit brighter , the
spot will appear to be brown .



RETINAL DISTRIBUTION OF COLORSPECIFIC NEURONS
The density of cones in the retina falls sharply
outside the fovea , but cones of all three
varieties are present , though in much smaller
numbers , all the way to the ora serrata .
The center of the fovea is unique both in having
the highest spatial density of cones and in
having a pure mosaic of red and green cones ,
with blue cones being eliminated from the
photoreceptor population within the central 1/8
degree of the visual field .
PECULIARITIES OF THE BLUE CONE
SYSTEM
 Both visual acuity and contrast sensitivity
are poorer in blue light than in red or green
light .
 This phenomenon is due not only to the
absence of short wavelength sensitive
cones in the foveal center but also to the
relative scarcity of blue cones , which are
much fewer in number in all retinal areas
than are middle wavelength sensitive or
long wavelength sensitive receptors .

COLOR ENCODING IN THE CEREBRAL
CORTEX
 The axons of color opponent and double
opponent cells , arising from somas in the
LGN , synapse with cells located in
several layers of the striate cortex .
 The first clue to color organization in the
primary visual cortex was the finding of
groups of cells that stain strongly for the
presence of cytochrome oxidase .
 These groups of cells are referred to as “
blobs “ .

The receptive fields of striate cortical cells
located between the blobs are
characteristically tuned to specific spatial
orientations , whereas cells within the
blobs have no apparent orientation
selectivity .
 Blob cells also have relatively simple ,
concentric , center-surround receptive field
properties , and strongly associated with
color differentiation .

It farther appears that the cells of
individual blob columns are devoted to one
or the other major types of color
opponency : red versus green or blue
versus yellow .
 Blobs devoted to red/green opponency
outnumber those of blue yellow
opponency by a ratio of about 3 to 1 .

In peristriate cortex ( area 18 or V2 ) rather
than blobs , the pattern of cytochrome
oxidase staining is one of parallel stripes
of alternating widths , thick and thin .

Cells within the thin stripe regions of
area 18 are not orientation selective ,
show a high frequency of color-opponency
, and probably receive their input directly
from blob cells of area 17 .




Cells in the thick stripes and in the pale
interstripe regions are orientation selective and
are frequently sensitive to binocular disparity (
probably concerned with stereoacuity .
The thin stripes of area 18 appear to receive
most of their input from the blobs of area 17
,while the pale stripes receive the majority of
their input from the interblob regions of area 17 .
Thus an anatomic and functional segregation of
form and color discrimination is maintained
through the striate and into the peristriate visual
cortex .
CONGENITAL DYSCHROMATOPSIAS
 Two broad groups are represented , those
in which reds and greens are confused
with one another and those in which blues
and yellows are confused .
 Congenital defects in color vision are
further subdivided into anomalous
trichromacy , dichromacy , and
monochromacy .

Anomalous trichromats are those who still
require three primaries in order to match
the full gamut of color but who do not
accept matches made by those with
normal color vision .
 Dichromats need only two primaries to
match any colored light within their
spectral range of vision , and will accept all
matches made by normals.

Monochromacy is a term used somewhat
confusedly , having been applied to two
different entities .
 Rod monochromats are those with a
complete congenital absence of cone
function , while blue cone monochromats
have no red or green cone function but
appear to have retinal pigments for both
rods and blue cones .

One or more of the normal cone pigments
are altered or missing altogether in
individuals affected by congenital
dyschromatopsia .
 Subjects with complete dichromacy have
only two types of cones , each having
normal spectral sensitivity characteristics ,
with the third type being absent .

Protanopes are dichromats having normal
green and blue cones , but an absence of
cones containing long wavelength
sensitive pigment .
 Conversely , deuteranopes have normal
red and blue cones , but an absence of
cones containing the middle wavelength
sensitive pigment .

While these subjects appear to have a
numerical component of cones, those
cones that should have contained a given
variety of pigment ,either red or green ,
have been genetically determined to
contain the complementary variety .
 Anomalous trichromats have three classes
of cones , containing three different
pigments , but the pigment in one of the
three has an abnormal spectral absorption
.

Protanomalous individuals , for instance ,
lack a normal red-sensitive pigment , but
instead have cones containing pigment
with a spectral absorption more nearly like
that of the normal middle wavelength
sensitive variety .
 As a consequence , the spectral
absorption curves of their red and green
cones are more nearly alike .

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
THE MOLECULAR BIOLOGY OF THE
CONGENITAL DYSCHROMATOPSIAS
Congenital dyschromatopsias of the most
common variety are caused by alterations in the
genes encoding the red- and green-sensitive
photopigments .
Color vision defects are produced by deletions
of red or green pigment genes or by formation of
hybrid genes comprised of portions of both red
and green pigment genes , resulting from an
unequal crossing over between genes that are
located in tandem within the X chromosome.




Differences in severity of the color vision defects
are related to variations in the cross over sites .
Even among color-normal trichromats , a certain
degree of polymorphism has been found .
Careful studies have shown that normal
trichromats can be further subdivided by the
patterns of the color matches that they make
with the Rayleigh anomaloscope .
Thus even among color-normals there are
detectable ,discrete variations in capacities for
discriminating between middle and long
wavelength light .
It is believed that most normal humans
have , in fact , more than three different
cone pigment types represented on the X
chromosome .
 The inherited dyschromatopsias are :
 1- binocular
 2- symmetrical
 3- and do not change over time .

HUE DISCRIMINATION TESTS FOR
CHARACTERIZING ABNORMAL COLOR
VISION .
 The Fransworth-Munsell 100 hue Test can
be used to estimate both the nature and
extent of defective color vision .
 The tests consists of a series of 85 colored
caps .
 The 85 caps are divided into four
approximately equal-sized groups that are
stored in separate boxes .

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
In the course of testing , a subject is asked to
arrange the caps in a linear sequence between
pairs of fixed reference caps that are located at
either end of each box .
Confusion between similar hues in patients with
congenital color defects result in characteristic
patterns in Fransworth-Munsell polar plots .
Transpositional errors are usually confined to
restricted zones within the color circle that are
located at directly opposite locations from one
another .
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
ACQUIRED DYSCHROMATOPSIAS
Acquired color vision defects , so called
dyschromatopsias , are different from congenital
color vision deficits in several respects .
Most importantly , acquired defects in color
vision are noticeable to the observer , whereas
congenital defects usually are not .
Additionally , acquired defects may be
monocular or markedly asymmetric and may
even vary from one part of the visual field to
another .
Acquired defects are commonly
associated with reduction in visual acuity ,
changes in dark adaptations , and/or
flicker discrimination .
 Acquired deficits are caused by a variety
of diseases that damage the retina , the
optic nerve , or the visual cortex .
 Toxic , vascular , inflammatory , neoplastic
, demyelinating , and degenerative
diseases are all well-recognized causes of
acquired dyschromatopsias .

CLASSIFICATIONS OF ACQUIRED
DYSCHROMATOPSIAS
 Three major types of acquired
dyschromatopsias called types I , II , and
III are included in this classification .
 The first two varieties are associated with
a major axis of hue discrimination in the
red – green region of the Fransworthmunsell diagram , much like the patterns
found for the protan and deutan varieties
of congenital dyschromatopsias .

Type I is protanlike , and is manifested as
an acquired loss of discrimination between
reds and greens with little or no loss of
blue- yellow discrimination .
 This variety of dyschromatopsia is also
associated with moderate to severe
reductions in VA .
 The type II dyschromatopsia is said to be
deutanlike , and involves mild to severe
confusion of reds and greens with a
simultaneous but milder loss of
discrimination between blues and yellows .




Again type II is usually associated with moderate
to severe reductions in VA.
The third type of acquired color vision defect in
the Verriest classification , type III , is said to be
tritan like , and is manifested by mild to
moderate confusions of blue and yellow hues
with a lesser or even absent impairment of red –
green discrimination . in this third type of
dyschromatopsia VA may be normal or only
mildly reduced .
HOW ACQUIRED DISEASES PRODUCE
THEIR VARIOUS PATTERNS OF COLOR
DIFICITS .
 Because of the small blind spot for blue
perception located at the center of the
visual field , human observers making
color judgments between the various caps
of the Fransworth-Munsell test must
depend on comparisons between the more
peripheral portions of the centrally viewed
test objects in oreder to distinguish hues in
the blue-yellow dimension of color space .

Diseases of the retina and optic nerve
produce characteristic patterns of damage
in the central and peripheral portions of
the visual field .
 For instance , the most common form of
glaucoma notoriously damages the
extracentral portions of the visual field , as
evidenced by sparing of VA until the latest
stages of the disease .




Apparently selective damage to blue – yellow
discrimination with relative preservation of redgreen discrimination and visual acuity ( type III
dyschromatopsia in Verriest classification ) is
common in chronic glaucoma .
This should be expected if damage to the
extrafoveal visual field ( outside the central half
degree ) exceeds that at the foveal center .
In this situation the higher degree of red-green
discrimination and visual acuity found in the
foveal cone mosaic will be relatively preserved ,
but the perifoveal blue cone contribution to color
discrimination will have been diminished .
THE CENTRAL VISUAL PATHWAY
 The ganglion cells are the only cells in the
retina that project from the eye to the
brain.
 Their axons terminate in a thalamic relay
nucleous called the leateral genicualte
body . postsynaptic neurons of lateral
geniculate body receiving retinal input
project in turn to the primary visual cortex .
 The retino-geniculo-cortical pathway
provides the neural substrate for visual
perception .

RETINAL GANGLION CELL TARGETS
 Although the lateral geniculate body is the
main target of ganglion cells , at least nine
other nuclei within the brain also receive
retinal input .
 The superior colliculus contains a
complete retinotopic map of the
contralateral field of vision .

Application of an electrical pulse to any
point on this retinotopic map evokes a
saccade of appropriate direction and
amplitude to shift fixation to the receptive
field location of neurons at the stimulation
site .
 Findings suggest that the superior
colliculus is important for visual orienting
and foveation but is not essential for
analysis of sensory information leading to
visual perception .




The pupillary light reflex is governed by a retinal
projection that exits the optic tract before the
lateral geniculate body to terminate bilaterally in
a scattered , ill-defined cellular complex within
the midbrain referred to as “ pretectal nuclei “ .
Neurons of pretectal nuclei send projections to
the epsilateral and contralateral EdingerWestphal subdivisions of the oculomotor nuclei .
Edinger-Westphal neurons provide
parasympathetic input via an interneuron in the
ciliary ganglion to control the sphincter pupillae
of the iris .
THE RETINO-GENICULO-CORTICAL
PATHWAY
 RETINA TO LATERAL GENICULATE
BODY
 The superb visual acuity of humans is
achieved at the fovea by thrusting aside all
retinal elements except the photoreceptors
, to minimize absorption and scattering of
light .
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This unique primate specialization requires
fibers from ganglion cells in temporal retina to
follow a circuitous route to the optic disc to avoid
passing over the fovea .
The horizontal raphe in the temporal nerve fiber
layer results in a complex , discontinuous
arrangement of ganglion cell axons at the optic
disc .
Cells in the temporal retina just above and below
the horizontal meridian send their fibers via a
roundabout route to enter the superior and
inferior poles of the optic disc respectively .
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Although their cell bodies are situated
close together in the retina , their fibers
are widely separated in the optic disc by
other fibers that directly enter the nasal
and temporal sides of the disc .
Retinotopic organization is further
complicated by intermingling between
peripheral and central axons as they
approach the optic disc .
 After leaving the eye at the optic disc , the
ganglion cell fibers become invested with
myelin to form the optic nerve .
 The retinotopic organization of ganglion
cell fibers is generally preserved within the
optic nerve .
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Near the eye the ganglion cell fibers are
precisely arrayed in a manner that
duplicates their arrangement within the
optic nerve head .
 Moving proximally toward the optic chiasm
the fibers gradually scatter in position until
the topography in the optic nerve becomes
quite imprecise .
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At least a third of the optic nerve is
comprised of macular fibers . near the
globe the macular fibers are clustered into
the central and temporal sectors of the
optic nerve , but more proximally they
intermingle with other fibers to distribute
throughout all sectors of the optic nerve .
At the optic chiasm the fibers originating
from ganglion cells located nasal to the
fovea cross into the contralateral optic
tract .
 Wilbrand observed that some crossing
fibers loop briefly into the opposite nerve
before entering the optic tract ( Wilbrand’s
knee ).
 At the chiasm the partial decussation of
optic nerve fibers merges input from the
two hemiretinas subserving the
contralateral field of vision .
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THE LATERAL GENICULATE BODY
The lateral geniculate body is the principal
thalamic nucleous linking the retina and the
striate cortex . the majority of retinal ganglion
cell fibers terminate in the lateral geniculate
body .
The nucleous consists of six principal cellular
laminae separated by thin cell-free zones .
Laminae 1,4,6 receive axons from the
contralateral nasal retina and laminae 2,3,5
receive axons from the epsilateral temporal
retina .
Each lamina of the LGB contains a precise
retinotopic map of the contralateral
hemifield of vision .
 Central vision is thought to be
represented, in the caudal , 6-layered
portion of the human LGB .
 Rostrally , the LGB is reduced to only 4
laminae by fusion of each pair of dorsal
laminae .
 The periphery of the visual field is
represented in this 4-layered region of the
nucleous .
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THE OPTIC RADIATION
 Neurons of the LGB complete the relay of
retinal input to the primary visual cortex by
projecting to the epsilateral occipital lobe .
 Their axons form a sheet of white matter
called the optic radiation .
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THE PRIMARY VISUAL CORTEX
 The upper and lower visual quadrants are
represented in the lower and upper
calcarine banks respectively , separated
by the horizontal meridian along the base
of the calcarine fissure .
 The fovea is represented at the occipital
pole .
 Most of primary visual cortex is actually
buried within the depth of the calcarine
fissure .
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The primary visual cortex contains a topographic
but highly distorted representation of the
contralateral hemifield of vision .
The most striking feature of the visual field map
is the enormous fraction of visual cortex
assigned to the representation of central vision .
Quantitative measurements in macaque monkey
reveal that between 55 and 60 % of the surface
area of primary visual cortex is devoted to the
representation of the central 10˚ of vision .
The linear cortical ( magnification factor ) –
the millimeters of cortex representing one
degree of visual field – has a ratio of more
than 40:1 between the fovea ( 0˚
eccentricity ) and the periphery ( 60˚
eccentricity ) .
 The representation of central vision is
highly magnified compared with peripheral
vision , so that the cortical area devoted to
the central 1˚ of visual field roughly equals
the cortical area allotted to the entire
monocular temporal crescent .
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The relatively magnified representation of the
macula in primary visual cortex furnishes an
important clue to how the cerebral cortex
analyzes sensory information .
The linear magnification factor of the retina is
equal to about 250 micrometers of tissue per
degree for all points in the visual field .
The linear magnification factor of the retina must
remain nearly constant , because the eye is
engaged in processing an optical image of the
visual environment .
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The steep gradient in visual acuity , from 20/20
centrally to 20/400 peripherally , is achieved by
variation in the density of cells in the ganglion
cell layer .
In central retina the ganglion cells are stacked 6
to 8 cells deep , declining to a broken monolayer
in peripheral retina .
Free of any optical constrains , the cerebral
cortex handles the richer flow of visual
information emanating from the central retina in
a different fashion .
The cortical mantle maintains uniform thickness
throughout the primary visual cortex but
allocates more tissue for the analysis of central
vision .
In the visual cortex the magnification factor
, rather than the cell density , varies with
eccentricity in the visual field
representation .
 From the fovea to the periphery of the
visual field a roughly parallel relationship
exists between cortical magnification
factor , ganglion cell density and visual
acuity .
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VISUAL FIELD EXAMINATION
 Vision may be impaired by damage to the
afferent visual pathway anywhere from the
retina to the occipital lobe .
 The preservation of topographic order
within the retino-geniculo-cortical pathway
usually allows accurate localization of
lesions causing a disturbance in vision by
careful examination of the visual fields .
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PRECHIASMAL LESIONS
 The crux of visual field analysis is to
decide whether a lesion is located before
,at, or behind the optic chiasm .
 A visual field deficit confined to one eye
must be due to a lesion anterior to the
chiasm involving either the optic nerve or
the retina .
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A visual field deficit in both eyes can result
from either bilateral prechiasmal lesions or
from a single lesion at or behind the
chiasm .
 Certain patterns of visual field loss are
characteristic of diseases that afflict the
optic nerve .
 Glaucoma selectively injures axons that
enter the superotemporal and
inferotemporal poles of the optic disc .
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This pattern of nerve fiber loss produces
arching , fan-shaped field defects that
emanate from the blind spot and curve
around fixation to terminate flat against the
nasal horizontal meridian .
 This type of field defect, known as Bjerrum
scotoma , mirrors the arcuate course of
fibers in the temporal retinal nerve fiber
layer .
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When the papillomacular bundle is
damaged , the patient develops a visual
field defect that encompasses the blind
spot and the macula .
 This field defect is called a cecocentral
scotoma .
 The cecocentral scotoma is typical of the
optic neuropathy caused by toxins like
ethanol , tobacco , methanol and
ethambutol .
 Inadequate blood supply to the optic disc
results in ischemic optic neuropathy .
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This condition is frequently accompanied
by an altitudinal pattern of visual field loss
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 CHIASMAL LESIONS
 The hallmark of chiasmal lesions is
bitemporal hemianopia .
 For reasons that remain quite unclear ,
crossed fibers are more vulnerable than
uncrossed fibers to compression of the
optic chiasm by mass lesions .
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The most common culprit is a tumor
arising from the pituitary gland within the
sella turcica .
 Lesions situated at the junction of the optic
nerve with the optic chiasm can produce
an anterior chiasmal syndrome consisting
of blindness in one eye and temporal
hemianopia in the other eye .
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POSTCHIASMAL LESIONS
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Any lesion behind the chiasm will produce
a homonymous hemianopia , namely a
visual field defect involving matching
portions of the overlapping temporal
hemifield of the contralateral eye and the
nasal hemifield of the epsialteral eye .
It is important to realize that visual acuity
will be entirely normal if the postchiasmal
pathway in the other hemisphere is intact .
 Input from only half the fovea is sufficient
for 20/20 Snellen visual acuity .
 A decrement in visual acuity should never
be attributed to a unilateral postchiasmal
lesion .
 As a general rule : the more congruent a
visual field defect,, the more posterior the
lesion in the visual pathway .
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Usually a lesion of the optic tract produces a
homonymous hemianopia with an afferent pupil
defect in the contralateral eye .
The afferent pupil defect in the contralateral eye
occurs because ganglion cells in the nasal
hemiretina outnumber those in the temporal
hemiretina .
Consequently , a lesion of the optic tract
damages more ganglion cell fibers driving the
pupil reflex of the contralateral eye the
epsilateral eye . this results in an afferent pupil
defect in the contralateral eye .
Small lesions of the superior colliculus
have been reported to produce an afferent
pupil defect in the contralateral eye with no
visual field defect in either eye .
 The lesion causes selective injury to the
asymmetric pupil fiber input to the
pretectum from the two hemiretinae .
 No field defect occurs because retinogeniculate fibers are entirely spared .
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An afferent pupil defect will develop after a
lesion of the optic tract , but should not develop
after a lesion of the lateral geniculate body ,
because axons governing the pupil reflex exit for
the midbrain well before the lateral geniculate
body .
Lesions involving the optic radiations or the
visual cortex do not result in homonymous
hemiretinal atrophy , because the primary
projection from the retina to the lateral
geniculate body remains completely intact .
Injury to just a portion of the optic
radiations occurs quite frequently and
usually produces a partial homonymous
hemianopia that appears roughly
quadrantic .
 For example , tumors of the temporal lobe
may selectively injure Meyer’s loop to
cause a homonymous inferior
quadrantanopia .
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Partial homonymous hemianopia also
occurs from lesions that damage only a
portion of the primary visual cortex .
 The conspicuous feature of an incomplete
cortical hemianopia is the extreme degree
of congruity . this congruity results
because axons from right eye and left eye
laminae of the LGB terminate side by side
in a finely dovetailed pattern of the ocular
dominance columns in visual cortex .
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MACULAR SPARING
 The extreme cortical magnification of the
macula is the key to understanding the
problem of macular sparing .
 In most individuals the vascular supply to
primary visual cortex is provided by the
posterior cerebral artery .after infarction to
the territory of the posterior cerebral artery
, a complete , macula-splitting
homonymous hemianopia ensues .
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However , in some patients the occipital
pole straddles the vascular territories of
the posterior cerebral artery and the
middle cerebral artery . in these patients
the occipital pole survives after posterior
cerebral artery occlusion , due to perfusion
by the middle cerebral artery .
Because the representation of central
vision is so magnified , the preservation of
posterior visual cortex spares tissue
devoted exclusively to macular vision .
 If only the occipital tip becomes infracted ,
the converse is produced : a homonymous
hemimacular field defect with peripheral
sparing .
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Complete bilateral injury or infarction of
the occipital lobes results in total blindness
. lesions of both optic nerves , tracts , or
the chiasm can also cause total blindness
.
 These two situations can be differentiated
by examination of the pupils .
 Pupillary responses to light will be absent
in patients with total blindness of
infrageniculate origin .
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STRUCTURE AND FUNCTION OF THE
LATERAL GENICULATE BODY
 In the nervous system afferent information
from every sensory system except
olfaction passes through the thalamus
before reaching the cerebral cortex .
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RECEPTIVE FIELD ORGANIZATION
 Cells in the visual system discharge action
potentials spontaneously even in the
absence of stimulation . For every cell this
spontaneous activity can be influenced by
stimulation with light in some region of the
visual field .
 This special zone is called “ receptive field
” of the cell .
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Neurons in the lateral geniculate body
share with retinal ganglion cells the same
basic center – surround arrangement of
their receptive fields .
 On- center cells respond with a burst of
spikes when a small spot of light
stimulates the field center .
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The maximal response is obtained by choosing
a spot size equal to the diameter of the receptive
field center .
If the spot is larger than the field center the cell’s
response is attenuated , indicating antagonism
between the center and the surround subfields .
A light annulus suppresses spontaneous activity
and produces a brisk “ off ” response.
The inputs of geniculate cells are wired together
to generate the more elaborate receptive fields
of cortical cells . Cells in visual cortex are
virtually unresponsive to stimulation with diffuse
light .
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Information about absolute light intensity is
generally not important for the visual system ,
except perhaps for the small subclass of retinal
ganglion cells that drives the pupil light reflex .
Information about spatial discontinuities in
patterns of light energy is more useful for image
analysis .
Cells with center- surround receptive field
organization are ideally suited for detecting such
contrasts .
Their best responses are elicited by contours
illuminating just a portion of their receptive field .
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SYNAPTIC INPUTS
Any given optic tract fiber arborizes exclusively
within a single geniculate lamina. Each axon
terminal plexus makes about a 100 synaptic
contacts over an area 50 to 100 micrometers
wide .
Each optic tract fiber may synapse with as few
as 4 to 6 geniculate cells and each geniculate
cell receives input from even fewer tract fibers .
A single spike from a retinal ganglion cell fiber is
sufficient to elicit a single spike from a geniculate
cell .
On-center ganglion cells trigger only oncenter geniculate cells and off-center
ganglion cells drive only off-center
geniculate cells .
 Some geniculate neurons derive their
excitatory input from only a single ganglion
cell. For the majority of geniculate cells the
excitatory input is provided by 2 or 3
ganglion cells .
 The lateral geniculate body contains about
1800,000 neurons .
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Approximately 90% of the retinal ganglion
cells terminate in the lateral geniculate
body , yielding a ratio of ganglion cell
fibers to geniculate neurons of 1:2 .
 This ratio is consistent with data
suggesting that each geniculate cell
receives input from 2 to 3 optic tract fibers
and that optic tract fiber contacts 4 to 6
geniculate cells . these average synaptic
ratios probably vary with eccentricity and
may differ slightly depending upon the
geniculate lamina in question .
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MAGNO VERSUS PARVO
 A striking difference is apparent in the
morphology of neurons in the dorsal
laminae and the ventral laminae of the
primate lateral geniculate body.
 The two ventral laminae contain loosely
packed cells with giant somas that exceed
30 micrometers in diameter .
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They are commonly referred to as the
magnocellualr laminae .
 The four dorsal laminae are comprised of
much smaller neurons and hence are
known as the parvocellular laminae .
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FUNCTIONAL SPECIFICITY OF
GENICULATE LAMINAE
 In the primate lateral geniculate body the
parvocellular laminae receive input from
the midget retinal ganglion cells , and the
magnocellular laminae receive input from
the parasol cells .
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This pattern of innervations implies that the
color-opponent and broad – band retinal
channels remain segregated at the level of the
lateral geniculate body .
In the parvocellular laminae the majority of cells
have color-selective responses .
Wiesel and Hubel described three principal
types of parvocellular units . the most common
cell ( type 1 ) has a standard center-surround
receptive field arrangement .
The center and surround have different spectral
sensitivities because they are fed by different
cone systems.
Parvo cells and mango cells differ in other
important receptive field parameters
besides their color responses .
 At any given eccentricity the receptive
fields of mango cells are several times
larger than the fields of parvo cells .
 Mango axons conduct action potentials to
striate cortex more rapidly than parvo
axons .
 Mango cells have higher contrast
sensitivity than parvo cells .
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To visual stimulation mango cells give rapid ,
phasic responses whereas parvo cells give slow
, tonic responses .
In parvocellular geniculate the on-center cells
and off-center cells are segregated into separate
laminae .
Laminae 5 and 6 receive input mostly from oncenter retinal ganglion cells and consequently
contain mostly on-center cells .
Laminae 3 and 4 receive input largely from offcenter ganglion cells and are more richly
populated with off-center cells.
This pattern of retinal innervation suggests
that one major function of the primate
lateral geniculate body isto sort retinal onoff channels into different laminae .
 However , on-center and off-center cells
are intermingled through out the
magnocellular geniculate laminae with no
loss of specificity in their inputs from oncenter and off-center parasol retinal
ganglion cells.
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A single excitatory postsynaptic potential from a
ganglion cell is usually sufficient to evoke a
discharge from a geniculate neuron .
There is a little divergence or convergence in the
transmission of information through the lateral
geniculate body . In all these respects the LGB
appears to behave as a relay nucleus .
The LGB receives a massive projection from
neurons in layer VI of the visual cortex. This
reciprocal corticogeniculate projection might be
expected to influence profoundly the receptive
fields of geniculate cells .
It offers an anatomic substrate for potential
modulation of retinal inputs at the
geniculate level before transfer to visual
cortex .
 However , reversible inactivation of the
cortico geniculate input by cooling striate
cortex produces only slight effects upon
the response properties of cells in the
lateral geniculate body.
 This surprising result leaves us without a
clear understanding of the role of the
lateral geniculate body .
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THE PRIMARY VISUAL CORTEX
 The primary visual cortex is often called “
striate cortex” referring to the prominent
stria found by Gennari .
 Later Brodmann parceled the cerebral
cortex into 47 different regions based upon
subtle distinctions in cortical histology .
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He assigned the arbitrary label of “ area 17
” to the primary visual cortex .
 In recent years other visual areas have
been discovered in extrastriate cortex
surrounding the primary visual cortex .
 The primary visual has received the
prosaic designation of V1 ( visual area 1
)and adjacent extrastriate visual areas are
named V2,V3,V4, and so on.
 Primary visual cortex , striate cortex , area
17 and V1 are all synonymous for the
same piece of tissue .
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OCULAR DOMINANCE COLUMNS
 In a tissue section of visual cortex stained
for Nissl substance the most striking
feature is the horizontal lamination of cell
bodies .
 There are six fundamental layers in the
primate cortex .
 In striate cortex some layers contain
multiple sublayers .
 Magno cells and parvo cells project to
separate layers of striate cortex in the
macaque monkey .
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Magnocellular axons terminate in layer
IVCα of striate cortex with minor branches
entering the deeper portion of layer VI .
 Parvocellular axons innervate layer IVCβ
and layer IVA , with small small additional
inputs to layer I and the upper portion of
layer VI .
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Layer IVA is absent in humans , indicating
that important differences exist among
similar primate species in the
cytoarchitecture of striate cortex .
 Axon terminals from right eye and left eye
geniculate laminae are not randomly
distributed in layer IVC of striate cortex ,
but rather , they are segregated into a
system of alternating parallel stripes called
ocular dominance columns .
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In humans the ocular dominance columns have
been revealed in striate cortex by examining the
distribution of cytochromoxidase .
Ocular dominance columns are absent in the
representation of the temporal monocular
crescent.
Ocular dominance columns are also lacking in
the cortical representation of the blind spot .
At the level of the LGB no binocular interaction
occurs , because retinal afferents terminate in
purely monocular laminae .
Convergence of afferents representing the
right eye and the left eye occurs only in
striate cortex .
 Binocular integration in the cortex is
delayed beyond the initial tier of synaptic
input by the segregation of geniculate
afferents into ocular dominance columns .
 Microelectrode recordings in macaque
monkey confirm that neurons in layer IVC
are strictly monocular .
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Cells that respond to stimulation from
either eye are found only outside layer IV .
such cells owe their binocularity to
convergence of inputs from monocular
cells in layer IV .
 The functional significance of ocular
dominance columns in humans and
macaques is uncertain
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PHYSIOLOGY OF STRIATE CORTEX
 Hubel and Wiesel were the first scientists
to provide a coherent description of the
receptive field properties of cells in striate
cortex .
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SIMPLE CELLS
 The receptive field of simple cells can be
mapped into excitatory and inhibitory
subdivisions with a small spot of light .
 They exhibit summation within their
separate excitatory and inhibitory subfields
and antagonism when both regions are
stimulated simultaneously .
 In these respects simple cells are similar
to the center-surround cells of the LGB.
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The critical distinction between geniculate
cells and cortical simple cells lies with the
spatial arrangement of their excitatory and
inhibitory domains .
 For cortical simple cells these domains are
not arrayed concentrically , , but organized
into parallel , flanking subfields separated
by straight boundaries .
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The geometry of subfields varies
considerably among simple cells . In the
most common layout a narrow elongated
region , either excitatory or inhibitory , is
sandwiched between two symmetric
subregions of the opposite type .
 Some cells have subfields of unequal area
and other cells have only two antagonistic
subfields .
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For all simple cells the best stationary
stimulus is a slit or bar of light exactly the
right dimensions to activate only an
excitatory ( on-response ) or inhibitory (
off- response ) subfield.
 Diffuse light evokes a meager response ,
because excitatory areas and inhibitory
areas cancel each other .
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Correct orientation of the light slit is crucial
to obtain the maximum response .
 If the stimulating light bar is not parallel to
the axis of the receptive field , it will
stimulate part of the inhibitory subfield and
fail to stimulate the entire excitatory
subfield .
 Orientation selectivity is thus a cardinal
feature of cortical simple cells .
 For the sake of illustration all the cells in
figure are depicted with a preferred
orientation of 45˚ .
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In fact , all orientations are represented
equally in the visual cortex .
 Simple cells also respond briskly to
moving bars , slits , or edges and
sometimes the discharge pattern can be
predicted from the arrangement of the
excitatory and inhibitory subfields .simple
cells usually fire a burst of spikes just as a
moving light slit enters an excitatory region
.
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The most vigorous discharge is provoked
by simultaneously leaving an inhibitory
zone and entering an excitatory zone .
 Cells with symmetric subfield
arrangements generally give an equal
response to movement in either direction .
 Cells with asymmetric subfields often give
unequal responses to movement in
opposite directions .
 The optimal speed of stimulus movement
can also vary among simple cells .
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COMPLEX CELLS
 The receptive fields of complex cells
cannot be mapped with stationary stimuli
into excitatory and inhibitory subregions .
 They give inconsistent on-off responses
when tested with stationary slits or spots
of light .
 However , when a light slit is swept across
the receptive field , it elicits a sustained
barrage of impulses .
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A complex cell may respond to movement
of the light stimulus anywhere within the
receptive field , provided the stimulus is
oriented correctly .
 By contrast , a simple cell fires only short
bursts at the moment when the light slit
crosses an interface between antagonistic
subregions .
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END-STOPPED CELLS
Ordinary complex cells show summation by
responding more robustly as the length of a light
stimulus is increased . the maximum response
occurs when a slit or bar equals the full length of
the cell’s receptive field.
Extending the stimulus beyond the length of the
receptive field augments the response no
further .
A special subtype of complex cell behaves in a
different fashion : the cell’s response declines
sharply as the stimulus exceeds the length of the
activating portion of the receptive field .
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RECEPTIVE FIELD HIERARCHY
Receptive fields undergo a remarkable transformation in
the progression from the LGB to striate cortex .
Cells in cortex respond best to suitably oriented bars or
edges , rather than circular spots , and their responses
depend critically upon the speed and direction of stimuli .
How do geniculate cells generate the receptive fields of
cortical cells ??
Simple cells are concentrated in layer IV of striate cortex
, the same cortical layer that receives the bulk of the
projection from the LGB . simple cells are also sprinkled
throughout layer VI , another layer innervated by
geniculate neurons .
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This finding is unlikely to be a coincidence : it
suggests that simple cells receive their input
directly from geniculate cells .
The axons of simple cells ramify widely to
synapse upon cells located in other cortical
layers .
Complex cells are common in all cortical layers
except layer IV . the logical inference is that
simple cells in layers IV and VI feed their input to
complex cells situated outside layer IV.
Hubel and Wiesel suggested that simple cell
receptive fields are constructed from geniculate
cell receptive fields .
For example , the simple field in the figure :
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Might be generated by excitatory input
from a row of geniculate cells with oncenters lined up as shown in the figure
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In such a scheme a light stimulus falling within
the narrow rectangular zone containing the
geniculate on-centers will elicit a net response ,
despite partial stimulation of antagonistic field
surrounds .
The inhibitory subfields of the simple cell might
drive from the off-surrounds of the geniculate
cells , or perhaps from off-center geniculate cells
placed in rows on either side of the on-center
units .
The receptive fields of complex cells are
probably built from simple cells that share the
same orientation tuning .
In one possible arrangement the receptive
fields of simple cells are concatenated
within the larger receptive field of a single
complex cell.
 A moving light slit will activate in
succession each simple receptive field ,
eventually exciting a discharge from the
complex cell .
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A stationary on-off stimulus elicits a feeble
response because activation of only one
simple cell is not enough to drive the
complex cell .
 The role of simple cells and complex cells
in visual perception is unclear , although
their receptive field properties are well
defined .
 Simple cells and complex cells respond
best to oriented contours , suggesting that
they process information about borders or
edges .
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MICROCIRCUIT OF PRIMATE STRIATE
CORTEX
A cortical module is comprised of a few million
cells. Each cortical module receives input from
only a few thousands geniculate fibers .
The ratio of cortical cells to geniculate afferents (
106 / 103 ) indicates that after relatively direct
transmission through the lateral geniculate body
, the retinal signal activates a cortical unit
containing approximately a thousandfold more
processing elements .
About 15% of the stellate cells in layer
IVCβ are inhibitory interneurons .
 Both mango and parvo geniculate fibers
send collaterals to pyramidal neurons in
layer VI . These pyramidal neurons also
receive geniculate input via apical
dendrites branching in layer IVC .

Layer VI pyramidal cells send axon
collaterals back to layer IVC , setting up a
reverberating intracortical circuit of
unknown function .
 The pyramidal cells in layer VI are also
believed to give rise to the major
reciprocal projection to the lateral
geniculate body .
 In summary , striate cortex receives
segregated input from two distinct
geniculate cell channels , mango and
parvo .

The parvo input goes via layer IVCβ to
layers II and III to supply cells within blobs
and between blobs . Blob cells and
interblob cells project to separate targets
in the next visual area , V2 .
 The mango input proceeds independently
from layer IVCα via layer IVB to V2.

EXTRASTRIATE VISUAL CORTEX
 According to the classical view , the striate
cortex performs a basic analysis of
geniculate input and then transmits some
critical essence to higher peristriate
cortical areas for further interpretation .
 Visual perception is thought to be
enshrined in two visual association areas
surrounding striate cortex , which
Brodmann called area 18 and area 19 .

Recent studies in monkeys using
physiologic recordings and anatomic
tracers have revealed that areas 18 and
19 together contain at least five distinct
cortical areas devoted to visual processing
: V2, V3 , V3A, V4 and V5 .
 Other visual areas within and beyond
areas 18 and 19 remain to be completely
mapped and characterized .

So far 25 cortical areas predominantly or
exclusively engaged in vision have been
identified in the macaque monkey .
 The striate cortex constitute the largest
single cortical area , averaging 1200 mm2
or about 12% of the neocortex .
 V2 , just slightly smaller than V1 , is the
second largest cortical area .

Together , V1 and V2 account for about
20% of the entire surface area of the
neocortex .
 After completion of initial processing in
striate cortex , visual information is
transmitted to areas V2,V3,V4 and V5 .
 Projections unite corresponding retinotopic
points in the visual field representation in
each of these cortical areas .

V2 and V3
V1,V2, and V3 are arranged to permit an
orderly topographic representation of the
visual hemifield in each area while contact
is maximized between adjacent cortical
areas
V2 and V3 have ventral and dorsal halves
that wrap around V1 , as a result the
superior and inferior visual field quadrants
are mapped in a retinotopic fashion in V2
and V3 .
 The cytochrome oxidase stain reveals an
array of coarse parallel stripes in V2





The stripes in V2 appear alternately thin and
thick , and extend along the full width of V2 from
the V1-V2 border to the V2-V3 border .
Thin stripes receive input from V1 cells located
within cytochrome oxidase blobs in layer II, III .
The thick stripes receive input from V1 cells
scattered through out layer IVB .
The pale interstripe zones that separate the thin
and thick stripes of intense cytochrome oxidase
activity get their input from V1 cells located
between the blobs in layers II ,III .
V4

This region has come to be known as the color
area in extrastriate cortex .
V5 ( middle temporal area )



Neurons in V5 were exquisitely sensitive to
stimulus motion .
Some units responded well to alight spot , bar ,
or slit moved briskly in a preferred direction and
gave no response to an opposite , null direction .
Directional selectivity of cells is such a singular
feature of V5 that it has been called the ( motion
area ) in extrastriate cortex .
VISUAL DEPRIVATION
 Amblyopia can be defined as a condition
caused by abnormal visual experience
during childhood resulting in unilateral or
bilateral decrease in acuity that cannot be
explained by a disorder of the eye itself .
 Without an ocular explanation for the low
acuity , ophthalmologists have speculated
that amblyopia is caused by anomalous
wiring of the eye’s central connections in
the brain .

INTRAUTERINE DEVELOPMENT
 In the human retina most of the ganglion
cells are generated between the eighth
and fifteenth weeks of gestation .
 The ganglion cell population reaches a
plateau of 2.2 to 2.5 million by week18 and
remains at that level until the thirtieth week
of gestation .
 After week 30 , the ganglion cell
population falls drastically during a period
of rapid cell death that lasts for about 6 to
8 weeks .

Thereafter cell death continues at a low
rate through birth and into the first few
postnatal months .
 The ganglion cell population is reduced to
a final count of about 1 million .
 The loss of more than a million
supernumerary optic axons may serve to
refine the topography and specificity of the
retinogeniculate projection by eliminating
inappropriate connections .

By week 10 the first retinal ganglion cell
fibers begin to invade the primordial
human lateral geniculate nucleus .
 In the macaque , Rakic has shown that
initially the inputs from each eye
intermingle to occupy the entire lateral
geniculate body .
 The segregation of ocular inputs occurs on
a parallel timetable with the development
of lamination .

Retinal afferents prune back their axon
terminals so that synaptic connections are
preserved only within appropriate
geniculate laminae .
 In the human fetus the geniculate laminae
emerge between weeks 22 and 25 .
 In the macaque monkey the cells destined
to comprise striate cortex are born
between days E43 and E102 . This period
corresponds to weeks 10 to 25 in the
human fetus .

In macaques the geniculate afferents
begin to innervate striate cortex by E110 ,
a time equivalent to gestational week 26 in
humans .
 Injection of anatomic tracers reveals that
initially the geniculate afferents
representing each eye overlap extensively
in layer IVC .
 The segregation of inputs into ocular
dominance columns transpires during the
last few weeks of pregnancy and is almost
complete at birth .


The maturation of the ocular dominance
columns requires thousands of left eye
and right eye geniculate afferents to
gradually disentangle their overlapping
axon terminals in striate cortex .
NEWBORN FUNCTION
 Any parent can testify that the visually
guided behavior of human newborns is
quite primitive .
 This observation implies that visual acuity
is still rather poor at birth .
 A number of methods are available to test
vision quantitatively in babies .

These techniques rely either upon visual
evoked potentials , optokinetic nystagmus
, or preferential looking by an infant toward
a patterned visual stimulus .
 Each technique exploits a different
approach to measure acuity , but all three
techniques agree fairly well that visual
acuity is only 20/400 at birth .

Visual acuity quickly improves to a level of
20/20 within the first few years of life .
 This rapid refinement in visual acuity is
paralleled by maturation of mechanisms
that control accommodation , stereopsis ,
smooth pursuit , and saccadic eye
movements.
 The human macula is immature at birth .
 The fovea is still covered by multiple cell
layers and only sparsely packed with
cones.

During the first year of life the
photoreceptors redistribute within the
retina and peak foveal cone density
increases by fivefold to achieve the
concentration found in adult retina .
 In newborns the white matter of the visual
pathway is only scantily clad with myelin .
 For the first two years after birth the myelin
sheaths enlarge rapidly .

Myelination continues at a slower rate
through out the first decade of life .
 At birth , neurons of the lateral geniculate
body are only 60% of their average adult
size .
 Their volume gradually increases until the
age of 2 years .
 In striate cortex refinement of synaptic
connections continues for many years
after birth .

THE ROLE OF ACTIVITY
 The visual system begins to form in utero
before visual experience can exert any
possible influence .
 The continued development of the central
visual pathways after birth suggests a
potential for postnatal activity to shape the
maturing visual system .

Apparently the basic elements of the
cortical module are generated before birth
, according to instructions that are innately
programmed .
 Surprisingly , physiologic activity in the
fetus plays a vital role in the development
of normal anatomic connections in the
visual system .
 In utero , mammalian retinal ganglion cells
discharge spontaneous action potentials
in the absence of any visual stimulation .

Abolishing these action potentials with
tetrodotoxin , a sodium channel blocker ,
prevents the normal prenatal segregation
of the retinogeniculate axons into
appropriate geniculate laminae .
 Intraocular administration of tetrodotoxin
also blocks the formation of ocular
dominance columns in striate cortex .


These experiments indicate that although
the functional architecture of the visual
system is ordained by genetics , the
specificity and refinement of connections
are molded by physiologic activity
occurring in the fetus .
EYELID SUTURE
 If a newborn monkey is reared in the dark
or with both eyes sutured closed , cells in
striate cortex eventually develop bizarre
receptive field properties .
 The cells lose sharp orientation tuning and
normal binocular responses .

Some cells become oblivious to visual
stimulation and can be detected only by
virtue of their erratic spontaneous activity .
 The remaining units give sluggish and
unpredictable responses to visual
stimulation .
 After a long period of deprivation , if the
monkey is introduced to a normal visual
environment ( or the eyelids are reopened
) , the animal is left profoundly blind with
minimal potential for recovery .

Cells in striate cortex do not recover
normal response properties .
 These laboratory observations
demonstrate that patterned visual
stimulation is required for a critical period
after birth to preserve and promote normal
visual function .

In ophthalmology an analogy can be
drawn with the newborn baby suffering
dense , bilateral , congenital lens opacities
. In this clinical situation the cataracts must
be removed soon after birth to avoid
permanent visual loss from bilateral
amblyopia.
 Cataract extraction delayed beyond the
critical period will not allow the child to
enjoy normal visual function .

If a monkey is visually deprived as an
adult by suturing closed both eyelids ,
there is no effect upon the properties of
cells in striate cortex .
 In adult patients , form deprivation induced
by slowly advancing cataracts does not
impair visual function in a permanent
manner .

After successful removal of the cataracts ,
the patient experiences full restoration of
sight .
 The occluded eye usually develops axial
myopia .In the lateral geniculate body the
cells in the deprived laminae become
slightly shrunken compared with the cells
in normal laminae .

Although cells within deprived laminae are
shrunken , they have normal centersurround receptive fields and respond
briskly to visual stimulation . These
findings imply that a defect at the level of
the lateral geniculate body is unlikely to
account for amblyopia .
 Monocular visual deprivation produces a
radical alteration in the ocular dominance
columns in striate cortex .


The ocular dominance columns of the
closed eye appear severely narrowed
when labeled with radioactive tracer .
THE CRITICAL PERIOD
 The conclusion from performing eyelid
closure in different animals at various ages
is that macaque monkeys are vulnerable
to the effects of eyelid suture for only a
few months after birth .
 This period is defined as the critical period
.

In the macaque monkey the closure of one
eye any time during the critical period
even for just a week , can result in the
shrinkage of ocular dominance columns
and the loss of the deprived eye’s ability to
drive cells in striate cortex .
 The critical period corresponds to a time
when the wiring of the striate cortex is still
malleable and hence vulnerable to the
effects of visual deprivation .

During the critical period the deleterious
effects of eyelid closure can also be
corrected by reverse eyelid suture .
 Reexapansion of deprived eye columns
does not occur if reverse suture is carried
out beyond the critical period .
 It may explain in part why patching in a
child to improve vision in an amblyopic eye
is fruitless if instigated after the end of the
critical period .

CLINICAL IMPLICATIONS
 The most common etiologies are unilateral
ptosis and cataract .
 In humans , patching of the normal eye is
the mainstay of treatment for amblyopia .
Recent clinical experience suggests that
good visual function can be achieved in
children with congenital monocular
cataract .

Effective therapy requires early surgical
removal of the offending cataract ,
appropriate refractive correction , and
vigorous patching of the normal eye .
 The critical period in humans has been
defined by documenting the visual
outcome in children after surgical removal
of congenital cataracts performed at
different ages .
 These studies indicate that the human
critical period extends for at least several
years after birth .

The duration of the critical period may also
vary according to the etiology of the
amblyopia .
 A minority of cases of amblyopia are
caused by media opacity . Other common
etiologies in children include strabismus . ,
anisometropia , nystagmus , and extreme
refractive error .


Raising an animal with alternate daily
occlusion of one eye using a translucent
contact lens leads to selective loss of
stereopsis with normal acuity in each eye
and this can be considered a special form
of amblyopia due to a breakdown of
binocular connections in striate cortex .
After cutting one extraocular muscle ,
some monkeys do not alternate fixation
but instead fixate constantly with the same
eye . The deviating eye invariably
develops amblyopia .
 Few cells in striate cortex can be driven by
stimulation of the amblyopic eye .
