EMBRYOLOGY OUTLINE
Formation of the Human Eye - Oyster
I. OVERVIEW: key principles
1. Embryogenesis begins with cell proliferation, cell movement, and changes in cell
shape.
a. proliferation is an increase in cell number by mitosis and division
b. motility is the ability of cells to move around and change shape
2. Specialized tissues are formed by collections of cells that have become specialized
themselves.
a. determination – the cells make a commitment to a particular developmental
path
b. differentiation – the cell begins to manufacture the proteins and intracellular
organelles necessary for the lifestyle to which it has been committed
3. Proliferation, movement, and differentiation in a cell group may require
communication with other cells.
a. Induction – the communication process between cells
4. The blastocyst forms during the first week of embryogenesis
a. cleavage – the earliest form of cell division in the embryo in which cells
become smaller at each division
b. morula – small cell cluster produced by the initial cleavage of the zygote, it
then becomes a blastocyst
c. blastocyst – ball of cells with a hollow interior (called a blastocoel)
d. inner cell mass – dense cell cluster on one side of the blastocoel
e. trophoblast – cells that surround the outside of the blastocyst
5. The inner cell mass becomes the gastrula, which is divided into different germinal
tissues
a. gastrula
b. epiblast – embryo forms from this layer cells
c. hypoblast – becomes the lining for the yolk sac
d. primitive streak – develops in the epiblast, defines it’s long axis at which cells
migrate down and laterally to form a three layered disc of cells
e. germ tissues – the three layers of cells in the gastrula are the primary germ
tissues
f. ectoderm – upper layer of cells closest to the amnion, will give rise to the
nervous system, epidermis, and other epithelial layers, and the major parts of
the eyes
g. mesoderm – middle layer of cells that will become blood vessels, muscle, part
of the urogenital system, bone , connective tissue, orbital bones, and
extraocular muscles
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h. endoderm – inner layer of cells next to blastocoel, forms lining of gut,
respiratory system, and related organs; no direct role in formation of eye and
orbit
6. Neurulation begins the development of the nervous system
a. gastrulation is followed by neurulation
b. neural folds – thickening of ectoderm
c. neural groove – separates neural folds
d. notochord – elongated column of cells formed by mesoderm
e. neural tube – tube of neural ectoderm that is the forerunner of the brain and
spinal cord
f. neural crest – cluster of cells from the roof of the neural tube that migrate out
to form peripheral nerve ganglia, corneal stroma and endothelium, trabecular
meshwork, iris stroma, and ciliary muscle
g. neural ectoderm – no longer connected to the surface ectoderm
7. Ocular development begins in the primitive forebrain
a. optic pits – beginnings of the eye, two small bumps on either side of the
neural tube
b. optic vesicle – cell proliferation of the optic pit produces large spherical
bulge, connected to the neural tube by a short, cylindrical optic stalk (both
vesicle and stalk made of epithelial cells, meaning they are hollow)
8. The optic vesicle induces formation of the lens
9. The optic cup and the lens form from different germinal tissues
a. lens placode – thickened region of the surface ectoderm from which the lens
develops
b. lens vesicle – the lens before its interior is filled with cells
c. optic cup – invagination of the lens placode
10. The optic cup is initially asymmetric, with a deep groove on its inferior surface
a. choroidal fissure – cleft along the underside of the optic cup that is the last
part of the cup to be completed
b. a primitive blood vessel the enters the fissure is also formed, and will
eventually become the hyaloid artery and then the central retinal artery
11. Closure of the choroidal fissure completes the optic cup
12. The lens vesicle forms in synchrony with the optic cup
13. The primitive lens is the first ocular structure to exhibit cell differentiation
14. All future growth of the lens comes from the early lens cells, some of which are
immortal stem cells
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a. stem cells - cells from which new cells of a particular cell type can be
produced
15. The precursors of the future retina, optic nerve, lens, and cornea are present by the
sixth week of gestation
16. In general, the eye develops from inside to outside
17. One or both eyes may fail to develop completely
a. degenerative anophthalmos – complete absence of the eye
b. microphthalmos – one or both eyes are significantly smaller than normal
18. Congenital absence of the lens may be an early developmental failure
19. Incomplete closure of the choroidal fissure can produce segmental defects in the
adult eye
a. colobomas – incomplete, improperly formed, or depigmented segments in
structures such as the iris, lens, ciliary body, choroids, and retina, either singly or
in combination
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Ocular Embryology
OVERVIEW: key principles
1. Embryogenesis begins with cell proliferation, cell movement, and changes in cell shape.
a. proliferation is an increase in cell number by mitosis and division
b. motility is the ability of cells to move around and change shape
2. Specialized tissues are formed by collections of cells that have become specialized themselves.
a. determination – the cells make a commitment to a particular developmental path
b. differentiation – the cell begins to manufacture the proteins and intracellular organelles
necessary for the lifestyle to which it has been committed
3.Proliferation, movement, and differentiation in a cell group may require communication with other
cells.
a. Induction – the communication process between cells, sometimes at a distance (not in direct
contact).
Keep in mind – the structures are described separately, however the events are happening
simultaneously.
I.
Germ Layer Development
A. Embryonic plate – during embryonic development (~3rd week) the primary germ layers
have formed in the embryonic plate.
B. Embryonic primary germ layers
1. Ectoderm – forms neural plate/numerous eye structures
2. Mesoderm – Globe/ orbit connective tissue
3. Endoderm – no ocular structures
C. Neural Plate
1. Thickening of ectoderm gives rise to CNS.
2. ~18 day – groove in neural plate forms ridges which grow into neural
folds.
3. ~22day – folds expand and grow toward one another forming neural
tube.
D. Neural Tube
1. Forms along the dorsal aspect of embryo.
2. Since the neural tube arises from ectoderm, the outer and inner linings of
the neural tube are the surface and neural ectoderms, respectively.
These lining have different locations anatomically and different
potentials for further development.
E. Neural Crest Cells and Mesoderm
1. Neural crest cells – an area of cells that separates from the ectoderm
on the crests of each of the neural folds. They then settle to lie
between neural tube and surface ectoderm.
2. Mesoderm – the middle embryonic layer is located between the neural
tube and surface ectoderm.
3. Mesenchyme – Neural crest cells and mesoderm form connective tissue of globe
and orbit
See figure 7.1 of Remington (page 104).
II.
Ocular structures and Lens Development
A. Optic Pits – Indentations on both sides of neural tube in forebrain region. Before
neural tube closes.
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B. Optic Vesicles - ~25days lateral, sac-shaped extensions are formed from optic pits.
After the neural tube closes, the vesicle wall is initially in contact with surface ectoderm
but is separated from it by cells of the neural crest origin and mesoderm. While it is in
contact with the surface ectoderm, it thickens and flattens to form the retinal disc.
C. Optic Stalk – invagination of optic vesicle and constriction of the tissue joining the
vesicle to the neural tube form the optic stalk. Inner surface cells are ciliated, and outer
surface cells are covered by basal lamina.
D. Optic, Embryonic, or Fetal Fissure – the lower wall of the optic vesicle and optic
stalk begin to buckle and move inward toward the upper and posterior walls which form
a cleft called optic, embryonic, or fetal fissure. Edges of the fissures grow toward
each other and begin to fuse after 5 weeks, fusion starts in the center an proceeds
anteriorly toward the rim of the optic cup and posterior along the optic stalk. Closure is
complete after 7 weeks forming the 2 layers optic cup.
E. Optic cup ~ 7 weeks. Composed of two layers separated by intraretinal space. Outer
layer –RPE, outer NPE of ciliary body, anterior iris epithelium. Inner layer – neural
retina, inner PE of ciliary body, posterior iris epithelium.
Flashback: Remember the pictures of the coloboma (incomplete iris) – this is where that initially
occurs – incomplete closure of optic fissure.
See Figure 7.2 -7.3 on pp. 105-106 of handout (Remington chapter).
F. Lens- development begins ~27 days (5 weeks). Invagination of the optic cup occurs
around the same time the surface ectoderm thickens around the optic vesicle and forms
the lens plate or lens placode. Thickening occurs by elongation of ectodermal cells by
regional increase in cell division.
G. Lens pit – invagination of the center of the lens plate forms the lens pit. Further
invagination forms the lens vesicle which pinches off from the surface ectoderm (~33
days) and becomes a hollow sphere of a single layer of cells surrounded by a basil
lamina. Upon further development, the basil lamina becomes the lens capsule.
H. Lens Capsule - ~5w. Evolves from the basement membrane of surface ectoderm and
lens epithelium secretions.
I. Embryonic nucleus and primary lens fiber cells – cells on the posterior side of the
hollow sphere, adjacent to the future vitreous cavity, elongate into the center of the
sphere to fill the empty space (lumen) within the lens vesicle. These epithelium cells
become primary lens fiber cells and form embryonic nucleus – no sutures. This makes
explains why there are only epithelial cells on anterior surface of the lens.
J. Sutures and Secondary Lens Fiber cells - ~7w.
Equatorial cells begin undergoing mitosis, elongation anteriorly and posteriorly around
the embryonic nucleus forming secondary lens fibers. 1st layer of secondary fibers is
complete after 7 weeks. Anteriorly, the secondary lens fiber cells meet and form
upright Y suture. Posteriorly, the secondary lens fibers meet and from inverted Y
sutures. These sutures are visible after the 3rd month. The region containing Y sutures
continues until birth forming the fetal nucleus.
K. Fetal Nucleus – the area of the lens containing the Y sutures (Both ant. And Post.)
L. Mitosis, cell elongation, and lens fiber formation continue throughout life.
M. FYI: At birth, lens has complete capsule with zonular fibers inserted, an anterior
epithelium, ~1.1 million lens fibers, and ~1300 lens shells, 6.5mm dia. An aged lens has
~ 3.6 million lens fibers and ~ 2500 shells, 9.5mm diam.
See figure 7.5 and 7.6.
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III.
Hyaloid Artery System (see figure 7.7 in handout)
A. Hyaloid artery – formed by a branch of the internal artery entering the optic cup
through the fetal fissure
B. It produces a network that fills the vitreous cavity and forms the posterior tunica
vasculosa lentis, which covers the posterior lens
C. Branches near the equator anastomose with the annular vessel, which sends loops
forward onto the anterior surface of the lens to form the anterior tunica vasculosa
lentis
i. Tunica vasculosa lentis – carries nutrients to the developing lens until
production of the aqueous begins
D. 9 weeks - hyaloid vasculature reaches its peak development, begins to atrophy, and is
reabsorbed during the 3rd and 4th months
E. 7th month – no blood flow is present in the hyaloid vasculature
IV.
Retinal Development (see figures 7.8, 9, 10 and 11)
A. Retinal Pigment Epithelium
i. The first retinal layer to differentiate
ii. Week 3 or 4 – cellular structures appear in the outer layer of the optic cup, and
pigmentation of the retinal epithelium occurs
iii. Week 6 – RPE is 1 cell thick – basal surface faces developing choroids and
apical surface faces inner layer of optic cup
B. Neural Retinal (figure 7.8 and 9 are very helpful in understanding this)
i. Week 4 or 5 – cells of the inner layer of the optic cup proliferate forming two
zones
ii. Cells accumulate in the outer region, the proliferative zone
iii. The inner marginal zone is acellular
iv. Week 7 – cell migration occurs – forms the inner and outer neuroblastic
layers
v. Week 8 - Ganglion cells and amacrine cells differentiate in the vitreal portion
of the inner neuroblastic layer – Muller cells also develop at this time
1. ganglion cells migrate, forming a layer close to the basement membrane,
and almost immediately send out their axonal processes
2. the bodies of the Muller and Amacrine cells remain in the inner
neuroblastic layer but move slightly towards the sclera
vi. Bipolar and Horizontal cells migrate from the outer neuroblastic layer and
settle near the Muller and Amacrine cells, eliminating the Transient fiber layer
(of Chevitz)
vii. By week 12:
1. Photoreceptor cells align along the outer side of the inner layer of the
optic cup
2. Horizontal, bipolar, amacrine and Muller cells are located in the inner
nuclear layer
3. Ganglion cell layer is evident
4. Inner and outer plexiform layers are filling with cytoplasmic processes
viii. Synaptic complexes begin to appear
ix. cone pedicles develop before the rod spherules - synapse with bipolar cells
before outer segments are completed
x. 6 months – dense accumulation of nuclei in the macular region
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V.
VI.
VII.
xi. 7 months – ganglion cells and cells of inner nuclear layer move to the periphery
of the macula
xii. Birth – a single layer of ganglion cells and a thin inner nuclear layer still covers
the foveal area – it is not until 4 months post partum, that the layers are
displaced to the sloping walls of the fovea, leaving the cones as the only neural
cell bodies in the center of the depression
xiii. The fovea is the last to reach maturity
C. Retinal vessels
i. Portions of the hyaloid artery within the optic stalk give rise to the central
retinal artery
ii. 4 months – vessels emerge from hyaloid artery near the optic disc and enter the
developing nerve fiber layer
iii. continue to develop but are not completed until 3 months AFTER birth
Cornea
A. Corneal epithelium
i. Arises form surface ectoderm
ii. Occurs at ~33 days
iii. All layers are present by 5th or 6th month
B. Corneal endothelium
i. Formed from first wave of neural crest that migrates into the space between the
corneal epithelium and the lens
ii. It is 1 to 2 cells thick by week 6
iii. 4 months – it is a single row and Descemet’s membrane begins to form – tight
junctions also begin to form
C. Corneal Stroma
i. Week 8 – second wave of neural crest migrates between developing epithelium
and endothelium – it splits and the posterior portion gives rise to the pupillary
membrane and the anterior portion gives rise to the stroma
ii. Rapid growth of the stroma causes an increase in curvature relative to the rest of
the globe
D. At 3 months – all layers of the cornea are present except for Bowman’s layer, which
develops during the 5th month
Sclera Development
A. Develops from neural crest mesenchyme
B. Development begins near the limbus and continues posterior until it reaches the optic
nerve
C. 3rd month sclera has surrounded developing choriod
D. 4th month lamina cribrosa begins to form
E. 5th month sclera is well differentiated
Uvea Development
A. Choroid (from back to front and inside to outside)
1. Develops from mesenchyme, starting near optic nerve
2. Mesenchyme and developing pigmented epithelium must be in contact for
choriocapillaris to form
3. At 2 months vessels appear
4. 5th month large and medium vessels are evident
5. At midterm of fetal development Bruch’s membrane is present
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6. Basement membrane is the last component to appear
B. Ciliary body
i. Outer layer of optic cup forms nonpigmented epithelium
ii. Inner layer of optic cup forms pigmented epithelium
iii. 3rd month Epithelium begins to form ridges which become ciliary processes.
iv. 4th month major arteriole circle is formed
v. 5th month Ciliary muscles begin developing
vi. 4-6 months Aqueous productions begins
C. Iris
i. End of 3rd month Optic cup begins to elongate and grows between the lens and
cornea.
ii. 5th month, Iris sphincter pulls away from pupillary zone of epithelium and
differentiates into smooth muscle
iii. 6th month, Iris dilator muscle fibers develop within epithelium
iv. Sphincter and Dilator muscles are completed by birth
v. Sphincter and Dilator muscles originate from neural ectoderm
vi. Anterior Border layer is formed from large gaps between Mesenchymal cells
vii. Pigmentation begins to appear at 10 weeks and is complete by 7 months
viii. Iris stroma forms from accumulation of collagen fibers
Pupillary Membrane – embryonic iris lacking a pupil
A. Develops from 2nd neural crest wave during 3rd month forms anterior border & stroma.
B. vascular network, anterior tunica vasculosa lentis joins to become iris vasculature
C. Joins with long posterior ciliary arteries.
D. Peripheral vessels contribute to minor arteriole circle of iris
E. Central vessels fragment and are reabsorbed into anterior border layer.
IX. Anterior Chamber
N. Trabecular Meshwork - ~4m – triangular neural crest cell mass becomes more and
more organized at 9m. well developed beams and pores are present.
O. Schlemm’s canal- derived from deep scleral plexus, tight junctions are present at 4m,
endothelium derives from neural crest that invades at 3 m.
X.
Vitreous (See Fig. 7-7 for vitreous development)
 Developing lens is crucial for vitreous accumulation
A. Primary vitreous – fills vitreal space in early development
 Made up of fibrils derived from the lens, retina, and hyaloid artery system
 Reaches its greatest extent by 2 months
 Vascular – will become Cloquets canal
 Cloquet’s canal- apex at optic disc and base at the posterior lens
o Well formed by the 4th month
o persists to adulthood
B. Secondary vitreous – forms around Cloquet’s canal (primary vitreous surrounding
atrophying hyaloid system)
 Avascular
 Contains fibril network and hyalocytes which are produced by the primary vitreous
C. Tertiary vitreous –an area between lens equator and ciliary body, not filled
 Some texts do not mention this at all.
VIII.
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XI.
XII.
 Once thought to give rise to zonule fibers that actually come from- thickening of
internal limiting membrane of the ciliary body which is formed by the ciliary
epithelium.
Optic Nerve – (See Fig. 7-15)
 Originates from the optic stalk
- Optic stalk connects the optic vesicle to forebrain
 As the optic stalk develops, an inferior invagination occurs giving rise to the optic
fissure
- The optic stalk becomes two-layered
- Outer layer becomes neuroglial sheath (surrounding the optic nerve) and
glial components of lamina cribosa
- Inner layer- vacuoles formed for retinal ganglion axons to pass through,
and other cells form optic nerve glial cells
 Ganglion cell axons fill the lumen of the optic canal
- Grow toward the central nervous system
 Nerve myelination begins at the lateral geniculate body during the 5th month, reaches
the chiasm during the 6th month and stops at the lamina cribosa 1 month after birth.
Ocular Adnexa
A. Eyelids - (See Fig. 7-16) At 2months surface ectoderms folds begin to grow anterior to
developing cornea. They meet and fuse ~ 10 weeks and remain fused until the lid
structures have developed. (See Fig. 7-17)
 Fusion of the eyelids protects the developing eye from amniotic fluid
- May also prevent keratinizing of the the cornea and conjunctiva
 At 5-6 months eyelids separate due to breakdown of desmosomes formed for lid
fusion (breakdown is possibly caused by Meibomian gland secretions
 Development of Eyelid Components
i. Surface ectoderm – skin and conjuctiva epithelium, hair follicles and cilia,
meibomian gland, Zeis glands, Glands of Moll
ii. Mesenchyme – orbicularis, levator, and tarsal muscles.
B. Orbit- (See Fig. 7-18)
 Bones fuse and ossify at 6-7 months.
 The angle between orbits decreases over time from initially 180° during early
development to 70° at birth and 68° at adulthood
- Globe reaches adult size by age 3
- Orbit reaches adult size by age 16
 Orbial fat and connective tissue originate from neural crest cells.
C. EOMS (Extraocular Muscles)- mesenchymal origin.
 Mesoderm forms muscle while connective tissue has neural crest origin.
 Recent studies seem to indicate the muscle origin, belly, and insertion grow
simultaneously
D. Nasolacrimal system – not well known
 Main lacrimal gland has a possible epithelium & mesenchyme origin
 Continues to develop after birth and is not fully developed until 3-4 years of age
 Drainage system – develops from surface ectodermal cord buried below maxillary
mesenchyme.
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