Chapter 9 Individual Organ
The Eye
1. The general shape, size and position of the eye
-
The eye is approximately a sphere 2.5cm
in diameter with a volume of 6.5ml.
-
It is parts of two spheres, a smaller one
anteriorly, the cornea which has a greater
curvature
than
the
sclera
which
constitutes a larger sphere.
-
Most complex of all sensory organs.
-
The front of the eye (cornea, pupil and
iris) are responsible for transmitting light
to the back of the eye. Damage to any of
these can result in various degrees of
impaired vision. The lens focuses light
rays onto the retina.
- The back of the eye (retina, macula and optic nerve) process the light images and transmit
them to the brain. The macula is particularly important for reading, because it is the area which
allows us to see fine detail. Damage to any of these also results in differing degrees of sight
loss. The vitreous is the clear, jelly-like substance which fills the middle of the eye. If the
pressure in the vitreous is too high it can also affect vision.
A. Cornea : no blood vessels, not many cells , inflammation is bad!!!
1. O2 from atmosphere, release of CO2
2. nutrients from inside the eye
3. moisture of the tear film
4. lubrication of the tear film
5. exchange of tears and the sweeping
action of lids
6. correct temperature, ph, etc
B. The Lens
- The lens is the clear part of the eye behind the iris that helps to focus light on the retina. The
lens is completely enclosed within a membranous capsule that contains a collagen that is rich in
glycosylated hydroxylysine residue. There are three major types of water soluble proteins in the
lens; crystalins, representing about 90% of the lens protein. In bovine, the -crystalins,
which constitute of 75% of the crystalins, consist of two chains A (173residue) and B (175
residue). During aging, the A and B chains become modified by partial proteolysis, with losses of
residues at the end of the chain, and by deamidation. These -crystalins that have modifiedA
and B chain s undergoes further aggregation (normally  8,000Kda) and result in the
development of gradually increasing opacity in the innermost part of nucleus (Cataract :백내장).
- Actin is present in the lens at 1-2% of total protein and may have a role in curvation of lens.
- The Lens has a low rate of metabolism (glycolysis and phosphogluconate oxidative pathway).
Lenticular carbohydrate metabolism is markedly impaired in diabetes, with excessive
accumulation in the lens of glucose, fructose, and sorbitol, and diminished ATP formation and
amino acid incorporation into lens protein. Sorbitol accumulation is an etiological factor in the
cataract of diabetes, exerting a hyperosmotic effect similar to that of galactose-induced
cataracts.
- The lens is one of the richest sources of glutathione. (Nucleus containing 600mg/100g tissue)
And other reducing agent, ascorbic acid, is present in lens in a concentration of  30mg/100g
tissue (almost 20times the plasma concentration)
- In early stage of senile cataract, [Na+]of lens increase while [K+] decreases. Then the [Ca++]
increase, which induced the lens swollen. The swollen lens loses protein, because of increase
in membrane permeability, proteolytic activity, and/or disruption of synthetic process. Amino
acids diffuse from the lens, and the lens became altered with formation of compact fibrous
aggregate.
C. Retina
The light-sensitive tissue lining the back of the eyeball; sends electrical impulses to the
brain. At the bottom is a photo of what an eye-care professional sees when looking at your
retina with an ophthalmoscope. The dark area near the center is the fovea . This area is actually
a depression in the retina. It is the retinal location of our best visual acuity and color vision. The
optic disc is the place where all the blood vessels and optic nerves converge and go out of the
retina to the brain. The optic disc, also called the blind spot, is where the axons of the ganglion
cells leave the retina to form the optic nerve. It is called the blind spot because there are no rod
or cone receptors in this part of the retina and we can not see objects that are imaged on this
part of the retina.
~ Optic Nerve head (Optic disc)
a. No receptors physiological blind spot
b. Point of exit of optic nerve
c.
Appears yellow compared to orange
Note: Histological Organization
Basic plan: Three layers
1. Outermost layer (tunica fibrosa). Tough connective tissue. Support/protection.
a. Cornea
b. Sclera
2. Middle layer (tunica vasculosa, uvea). Vascular and heavily pigmented.
a. Choroid b. Ciliary body c. Ciliary process d. Iris
3. Inner layer (tunica interna). Retina: photoreceptors located here.
a. Neural retina: 10 traditional histological "layers."
1. Pigmented layer of retina proper: layer 1.
2. Nervous layers of retina proper: layers 2-10.
b. Non-neural anterior portion forms posterior aspect of iris and ciliary body.
THE RETINA: 10 traditional histological layers
1. Pigment epithelium layer: (derived from outer layer of optic cup): Functions in absorbing
scattered light rays; phagocytosis of worn out discs shed from rods; stores and releases vitamin
A to photo receptors. Hereditary retinal dystrophy: inability of PE to phagocytize worn out discs.
Pigment epithelium closely adheres to choroid rather than rest of retina. Potential space exists
between pigment epithelium and rest of retina (from embryonic development). Trauma can
dislodge retina (i.e., layers 2-10) at this site: detached retina.
2. Layer of Rods and Cones: (photoreceptors: outer
and inner segments) Renewal of photoreceptor elements:
the outer discs of old rods are shed into potential "space"
between outer segments and pigment epithelium which
phagocytoses them. New discs are made from below and
move upward, replacing the old. Cones discs are shed
and replaced more slowly.
3.
External
limiting
membrane:
specialized
desmosome-like junctions between modified glial cells of
retina (Muller cells) and photoreceptors. Appears like line
at light microscope level.
4. Outer nuclear layer: cell bodies (and nuclei) of rods
and cones (photoreceptors).
5. Outer plexiform layer: synapses between "axons" of
rods and cones, bipolar neurons & horizontal cells. HC
are association neurons that are involved in local
processing of visual information in the retina.
6. Inner nuclear layer: cell bodies of bipolar cells
(neurons). Bipolar neurons receive abundant synapses
from rods and cones, are the main secondary link in
transmission of visual information.
7. Inner plexiform layer: synapses between bipolar and
ganglion cells and amacrine cells. AC are association
neurons that are involved in local processing of
information in the retina.
8. Ganglion cell layer: cell bodies of ganglion cells, the
output cells (neurons) of retina. Ganglion cells receive
abundant synapses from bipolar neurons, and are the
third main link in transmission of visual information. True
action potential generated here.
9. Nerve fiber layer: the axons (unmyelinated) of retinal
ganglion cells follow curvature of retina to exit at optic
disc. Become the optic nerve (myelinated) outside the
retina.
10. Internal limiting membrane: expanded ends of
modified glial cells of retina (Muller cells) and basement
membrane directly adjacent to vitreous. Appears like line
with light microscopy.
Main layers/cells concerned with reception and transmission of light signal:
1. Layer of rods and cones receive and transduce light signals. (Receptor potential.
Hyperpolarizing.) Transmit to bipolar neurons.
2. Inner nuclear layer - bipolar cells. (Slow graded potential.) Transmit to ganglion cells.
3. Ganglion cell layer (First place in visual transmission chain where true action potential
is generated.) Transmit to brain.
Rod Cell, Cone Cell
The
light
sensing
neurons
in
the
retina
are
called
photoreceptors. These neurons contain the photo-pigment
that can detect photons of light. Different animals have
different types of photoreceptors with different sensitivities to
light. Primates (including humans) have both rod and cone
cells. Cone cells are used in color vision and there are three
types that are sensitive to different wavelengths of light, red,
blue and green.
Rods: Rods detect dim light as they have a high sensitivity
due to a high concentration of photo-pigment. Rods contain
only one type of photo-pigment or rhodopsin. Rods can
amplify the light signal better than cones but saturate quickly.
Therefore rods are used for night/dim light vision whereas
cones are used for daylight vision. Rods have low accuracy
and are not present in the fovea. Rods outnumber cones by
20:1.
Cones: Cones have a lower sensitivity than rods and are
specialized for day light vision. Cones cells only saturate in
intense light. The cone cell system is highly accurate and
used for visual acuity, therefore found concentrated in the
fovea. They contain less photo-pigment. One cone cell
contains only one type of photo-pigment or rhodopsin which
can be either red, green or blue.
Structure of the rod or cone cell: Each rod or cone cell has an outer and inner segment. The
outer segment is characterized by many layers of membranes stacked like discs on top of one
another. The light detecting photopigment is found concentrated in these specialized
membranes. Each membrane is packed with pigment; in rod cells there are 100 million pigment
molecules per cell. This dense packing in layers increases the probability that a photon will be
detected by the photoreceptor cell.
Photopigment (rhodopsin = retinal + opsin): The opsin molecule is highly conserved
between all animals and belongs to the "super"-family of 7 transmembrane proteins that are
coupled to G proteins. Rather than being activated by a neurotransmitter or chemical these
proteins are activated by light. This is because the opsin protein is tightly associated with retinal
(a vitamin A derivative, (so eat your carrots!)). Together opsin + retinal is known as rhodopsin.
In the dark retinal is in the 11-cis form but if activated by a photon of light then the retinal
immediately switches to the all-trans form (within pico-seconds).
The switch in the retinal causes a protein conformational change in the rhodopsin protein to a
form called metarhodopsin which in turn activates a G protein. The G protein in the vertebrate
photoreceptor cell is called transducin. When the transducin is activated the
to GTP and releases the
subunit. The
subunit now binds
subunit now is free to interact and activate its target
which is a phosphodiesterase. The now active phosphodiesterase hydrolyzes cGMP to GMP
and therefore the ultimate consequence of this cascade is to reduce the level of cGMP in the
cell in the presence of light.
The photoreceptor cells of vertebrates contain a cGMP-gated cation (Na+) channel.
This channel has been cloned and is similar to the channel found in the
olfactory system. It doesn't inactivate and is non-selective, Na+, Ca+2 and K+.
This channel is open and active in the dark when the levels of cGMP are high. Therefore in the
dark the membrane potential of the photoreceptor cell will be about -40 mV. (dark=depolarized)
In the light there is a dramatic reduction in the level of cGMP as a result of the cascade
described above such that the cGMP-gated channel is closed. Therefore the leak K+ channel
will dominate and now the membrane potential will be about -70 mV.
What is the point of the cascade? The G protein to phosphodieterase cascade allows for
amplification of the reponse. A single molecule of rhodopsin can diffuse within the disc and
activate hundreds of G proteins each of which activates a phosphodiesterase. Each
phosphodiesterase is capable of hydrolyzing 1000 cGMP molecules per second. Therefore in a
rod cell one photon of light can result in the closing of 300 cGMP-gated ion channels (3-5% of
the total). As the light stimulus increases there is a matching increase in the degree of
hyperpolarization. Again in this sensory system the intensity of the stimulus can be converted to
an electrical signal (in this case a hyperpolarization instead of a depolarization).
PDE: phosphodiesterase
RGS: regulators of G protein signaling
G protein b subunit, G5L
Formation of Rhodopsin
Regeneration of rhodopsin from opsin and 11-cis-retinal occurs spontaneously, but since
trnas-retinal is formed on breaching, mechanism for regeneration of the cis form are required.
As summarized bellow, retinal is reduced to retinol by dehydrogenase and an isomerase
converts trans-retinol to cis-retinol in the retina.
C19H27CH2OH + NADP+
Retinol
=====
C19H27CH=O + NADPH + H+
Retinal
Rhodopsin
LIGHT
Retinal isomerase
Opsin + 11-cis-retinal
trans-retinal + Opsin
Dehydrogenase
11-cis-retinol
trans-retinol
RBP
Blood
RBP-trans-retinol
+RBP
Liver
Esterase
trans-retinol
H2O + trans-retinylpalmitate
(storage form)
Palmitate