The eyes develop from four sources during the 22nd day of intrauterine life. Optic grooves form on the forebrain which become optic vesicles that induce lens placodes in the surface ectoderm. The vesicles and placodes invaginate to form the optic cup and lens vesicle. The optic cup differentiates into the neural retina while the lens vesicle forms the lens. The surrounding mesenchyme develops into supporting structures like the choroid, sclera, cornea and vitreous body. Key genes like PAX6 and SHH regulate eye development through epithelial-mesenchymal interactions between the optic cup and surrounding tissues. Abnormalities can result in conditions like coloboma, catar

1. Development of Eye Dr. Piyush Kumar

2. Introduction

3. Embryological development
A B

4. C D

5. E F

7. ❖ The eyes are derived from four sources:
❖ Neuroectoderm of the forebrain
❖ Surface ectoderm of the head
❖ Mesoderm between the previous two layers
❖ Neural crest cells

8. ❖ On the 22nd day of intrauterine life a pair of shallow Optic
grooves appear on the sides of forebrain neuroectoderm.
❖ As cranial neuropore closes; grooves form outpouchings
called optic vesicle.
❖ Vesicles subsequently come in contact with the surface
ectoderm and induce changes in it forming lens placode.
❖ Vesicle and placode begin to invaginate.
CBA

9. ❖ Invagination of optic vesicle causes the formation of a double walled
optic cup.
❖ Initially has a lumen called intraretinal space, later disappears due to
apposition of both walls.
❖ Invagination is extended to the inferior surface of cup forming choroid
fissure.
❖ Fissure allows the hyaloid artery to reach the inner chamber of the eye.
❖ Lips of the choroid fissure fuse, and the mouth of the optic cup becomes a
round opening, the future pupil.

10. ❖ Invagination of lens placode forms the lens vesicle.
❖ Lens vesicle loses contact with the surface ectoderm and
lies in the mouth of the optic cup.
❖

11. Formation of different parts of eye
❖ Formation of retina, iris & ciliary body:
❖ Outer layer of optic cup forms pigment layer of retina.
❖ Posterior 4/5th of inner layer (neural layer) is called pars optica
retinae and it differentiates into three layers.

12. ❖ Photoreceptive layer:
bordering the intraretinal
space. This layer differentiates
into rods and cones.
❖ Mantle layer: gives rise to
neurons and supporting cells,
including the outer nuclear
layer, inner nuclear layer, and
ganglion cell layer.
❖ Fibrous layer: axons of nerve
cells, which converge toward
the optic stalk, and form the
optic nerve

13. ❖ Anterior 1/5th of neural layer called pars ceca retinae, remains one cell layer thick which
later divides into:
❖ Pars iridica retinae: form the inner layer of the iris.
❖ Pars ciliaris retinae: form cilliary epithelium.
❖ The region between the optic cup and the overlying surface epithelium is filled with
loose mesenchyme.
❖ Inside this tissue sphincter and dilator pupillae of iris is formed from underlying
neuroectoderm.

14. ❖ The loose mesenchyme in the region of pars ciliaris
retinae forms cilliary muscles.
❖ A network of elastic fibers, the suspensory ligament or
zonula connects ciliary body to lens.
❖ Contraction of the ciliary muscle changes tension in the
ligament and Controls curvature of the lens.

15. ❖ Development of lens:
❖ Cells of the posterior wall of lens vesicle elongate
anteriorly and form long primary lens fibers that
gradually fill the lumen of the vesicle.
❖ Secondary lens fibers are continuously added to the
central core.

16. ❖ Development of Choroid, Sclera and Cornea:
❖ The loose mesenchyme surrounding developing eye differentiates into an
inner layer comparable with the pia mater of the brain and an outer layer
comparable with the dura mater.
❖ The inner layer later forms a highly vascularised pigmented layer known as
the choroid.
❖ The outer layer develops into the sclera and is continuous with the dura
mater around the optic nerve.

17. ❖ In the anterior part; vacuolisation occur in the mesenchyme splitting it
in outer layer and inner layer and the cavity in between is anterior
chamber.
❖ Outer layer is substantia propria of cornea and is continuous with
sclera.
❖ Inner layer is iridopupillary membrane, which disappears completely.
❖ Anterior chamber is lined by flattened mesenchymal cells forming the
inner epithelial lining of cornea.
❖ Outer epithelium of cornea formed by surface ectoderm.

18. ❖ Development of Vitreous body:
❖ Mesenchyme has also invaded the inside of the optic cup
through choroid fissure.
❖ It forms the hyaloid vessels, which during intrauterine life
supply the lens and form the vascular layer on the inner
surface of the retina.

19. ❖ It also forms a network of fibers between the lens and retina.
❖ The interstitial spaces of this network later fill with a
transparent gelatinous substance, forming the vitreous
body.
❖ The hyaloid vessels in this region are obliterated and
disappear during fetal life, leaving behind the hyaloid canal.

20. ❖ Development of optic nerve:
❖ The optic cup is connected to the brain by the optic stalk
❖ Choroid fissure present on its ventral surface has the hyaloid vessels.
❖ The nerve fibers of the retina returning to the brain lie among cells of
the inner wall of the stalk.
❖ Choroid fissure closes in 7th week.
❖ Number of nerve fibre continuously increase obliterating the lumen.

21. ❖ Cells in inner layer wall form neuroglial cells supporting optic nerve.
❖ The outer layer of the optic stalk becomes the neuroglial sheath that
surrounds the optic nerve; it also gives rise to the glial components of the
lamina cribrosa.
❖ The optic stalk is thus transformed into the optic nerve.
❖ The hyaloid vessels, trapped in the optic stalk form the central retinal
vessels.
❖ On the outside, a continuation of the choroid and sclera, the pia arachnoid
and dura layer of the nerve, respectively surround the optic nerve.

22. Molecular regulation
❖ Key regulatory gene is PAX6.
❖ Initially PAX6 transcription factor is
expressed in the anterior neural ridge of the
neural plate before the neurulation begins.
❖ PAX6 establishes a single eye field that later
separates into two optic primordia.
❖ signal for separation of this field is SONIC
HEDGEHOG (SHH) expressed in the
prechordal plate.
❖ SHH upregulates PAX 2 expression in the
optic stalks while downregulating PAX6,
restricting this gene’s expression to the optic
cup and lens.

23. ❖ Epithelial-mesenchymal interactions between prospective lens ectoderm,
optic vesicle, and surrounding mesenchyme then regulate lens and optic
cup differentiation.
❖ FGFs from the surface ectoderm promote differentiation of the neural
(inner layer) retina,
❖ TGF-β secreted by surrounding mesenchyme, directs formation of the
pigmented (outer) retinal layer.

24. ❖ Downstream from these gene products, the transcription factors MITF and
CHX1O are expressed and direct differentiation of the pigmented and neural
layer, respectively.
❖ Differentiation of the lens depends on PAX6 expression.
❖ PAX6 upregulates the transcription factor S0X2 and also maintains PAX6
expression in the prospective lens ectoderm.
❖ In turn, the optic vesicle secretes BMP4, which also upregulates and maintains
S0X2 expression as well as expression of LMAF, another transcription factor.

25. ❖ Next, the expression of two homeobox genes, SIX3 and PROX1 is
regulated by PAX6.
❖ The combined expression of PAX6, S0X2, and LMAF initiates expression
of genes responsible for lens crystallin formation, including PROXl.
❖ SIX3 also acts as a regulator of crystallin production by inhibiting the
crystallin gene.
❖ Finally, PAX6, acting through F0X3, regulates cell prolifera- tion in the
lens.

26. Applied
❖ Coloboma: failure of closure
of the choroid fissure.
Normally closes in 7th week.
If cleft persists usually only
in iris called coloboma iridis.
❖ Persistant iridopupillary
membrane:

27. ❖ Congenital cataract: lens
opacity caused in
intrauterine life. Causes may
be genetic, congenital rubella
syndrome or a few metabolic
disorders.
❖ Microphthalmia: less than
2/3rd of the volume of a
normal eye. Common causes
include TORCH infection.

28. ❖ Anophthalmia: absence of eye
❖ Aphakia : absence of lens
❖ Aniridia : absence if iris
❖ Cyclopia/ synophthalmia: single or fused eyes.

29. ❖ Langman’s medical embryology.
❖ Keith L. Moore. The developing Human.
Bibliography

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