ABHILASH RANJAN ROLL NO - 02

Eye development commences around 22nd day; embryo has 8 pairs of somites and 2mm in length.

Develops from neural tube, epidermis and periocular mesenchyme.

Neural folds commence fusion to form neural tube; bt before their complete fusion caudally and rostrally optic sulci appear as shallow pits on the inner aspect of neural fold. START OF WEEK 4
Day 22(2-3 mm)

By day 25(20 somite stage) hollow optic vesicle enlarges and becomes fully ensheathed by the mesenchymal cells except at the apex of vesicle. Apex vesicle is closely apposed to surface ectoderm.

END OF WEEK 4
Day 27(4-5 mm)

Optic vesicle

RETINAL DISC (future neural retina) lies beneath surface ectoderm which on 27th day recognised as LENS PLACODE.

At this stage just before complete closure of neural tube, n. ectoderm grows outward and form spherical optic vesicle. The optic vesicle connected to forebrain via o. stalk.

Optic Vesicle stage

Start of wk. 4 to end of wk. 4

Start of week 5 Optic Cup stage

Start of wk.5 to end of wk.8

Start of week 6

Figure 4: Development of the eye. (A) Evagination of the primary optic vesicle. (B) Invagination of the surface epithelium and formation of the optic cup by invagination at the embryonic fissure. (C) Detachment of the lens from the surface epithelium. (D) The ciliary region and iris are formed from neuroectoderm, and the lens from the posterior cells of the lens vesicle. (E) The completed eye. IPE, iris pigmented epithelium; RPE, retinal pigment epithelium; CB, ciliary body.

As the optic vesicle invaginates to form optic cup the original outer wall of the vesicle approaches its inner wall. The invagination of the ventral surface of the optic stalk and of the optic vesicle occur simultaneously, creating a groove called optic fissure. The margins of the optic cup then grow around the optic fissure. The lens plate invaginates to first form a cup and a hollow sphere called lens Vesicle. Vascular mesoderm enters the optic stalk and eventually forms hyaloid system of vitreous cavity.

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START OF WEEK 7

Development of the eyelids. A, Seventh week: upper and lower eyelid folds grow over the eye. B, Eyelids fuse during the eighth week. Fusion starts along the nasal margin. C, As cilia and glandular structures develop, eyelids gradually open from the fifth to the seventh month.

START OF WEEK 8

DEVELOPMENT OF RETINA
By the end of 8th week retina is differentiated into a thin outer layer which forms the retinal pigment epithelium (RPE) and much thicker inner neural retina. These layers are continuous at the optic cup margin. Invagination of optic cup leads to obliteration of optic ventricle or sub retinal Space. Neural retina lies adjacent to RPE. In 8th week ganglion cell axons grow from inner retina towards the optic stalk Forming optic nerve.

The surface of subretinal space is ciliated; the cilia of the neural retina form rods and cones whereas the cilia of RPE degenerate. Mesenchyme derived from neural crest cells condenses around outer surface of optic cup The innermost layer of mesenchyme is loose and highly vascular which forms the choroid. Homologous with pia and arachnoid mater of brain. The outer condensed layer will form sclera, homologous to dura mater of optic nerve and brain.

Typical inferonasal coloboma of the optic nerve head, retina, and choroid.

DEVELOPMENT OF CORNEA
The surface ectoderm which seals over the lens pit forms future corneal epithelium.

Around day 33 the first wave of mesenchymal cells which passes over the optic cup margin migrates centripetally in the space between the anterior surface of the lens and the surface ectoderm to form the corneal endothelium.
Around day 49 the second wave of mesenchyme penetrates the space b/w the basal surface of corneal epithelium and endothelium to form corneal stroma. Around 8 weeks collagen fibres alongwith synthetic fibroblasts are seen which are called as fibroblasts.

By this time the endothelium ultimately becomes a simple squamous layer from a double layer and lies on a thick basal laminathe precursor of descemets membrane
Bowmans membrane becomes identifiable by 5 months as an acellular collagenous zone beneath the epithelium

During the course of development the stromal collagen bundles become organised into highly oriented lamellae and keratobalsts mature into keratocytes. This process Occurs first in posterior or deeper layers then in superficial or anterior layers. Cornel transparency is attained before birth owing to maturation of superficail lamellae and hydration activity of endothelial cells.

Congenital hereditary corneal dystrophy with characteristic uniform ground glass edema from limbus to center of cornea

DEVELOPMENT OF LENS
Ectodermal cells form lens placode by 27 days.

By 29 days ectodermal cells invaginate to form a lens vesicle with a central depression called the optic pit.
By 33 days the lens vesicle detaches from the surface ectoderm and sinks into the underlying rim of optic cup. Under the inductive signal(fibroblast growth factor) from developing neural retina The posterior cells of lens vesicle elongate to form the primary lens fibre. The base of each elongating lens cell remains attached to the basal lamina posteriorly and their apices grow toward anterior lens epithelium, thereby obliterating the lens cavity. Subsequent lens fibre arise from the anterior lens epihelium at the equatorial zone and are known as secondary lens fibres.

The tips of the secondary fibres meet the primary fibres at the Y-shaped anterior and posterior lens sutures. The basal lamina encases the lens in a membranous noncellular envelope the lens capsule secreted by the lens epithelium on its external aspect. CONGENITAL CATARACT

DEVELOPMENT OF UVEAL TRACT

THE CILIARY BODY
Development commences at 11-12th week with indentation of the outer pigmented layer of neuroectoderm near the optic cup rim by small capillaries in mesenchyme. Initially the inner non pigmented ciliary epithelium is flat, but as the vascular sprouts enlarge they push inwards to form primitive radial folds. During the course of time pars plana separates primitive neural retina and ciliary Folds. The ciliary epithelium commences aqueous production by 20 weeks. The ciliary muscle differentiates at 15 weeks from the mesenchyme b/w neuroectoderm and scleral condensation external to the early ciliary folds

THE IRIS

At around 14 weeks the optic cup neuroectoderm grows in a centripetal manner b/w The mesenchyme that has formed the cornea and the anterior lens surface. This incorporates some of the vessels of pupillary membrane and forms the iris stroma. Sphincter and dilator pupillae muscles develop directly from neuroectoderm. Sphincter pupillae differentiation commences before dilator pupillae. The dilator pupillae muscle develops around 6 months as basal extensions of pigmented epithelial layer of iris. During dev. the posterior iris epithelium is largely amelanotic. Intracytoplasmic melanin increases in 4th month initially near the pupillary margin. By 7-8th month this layer is heavily pigmented and the posterior layer loses its pigment.

ANIRIDIA

Autosomal dominant b/l disease; apparent absence of iris. A misnomer bcoz histologically iris is seen as an abnormal stump of hypercellular stroma. Also associated with ectopia lentis,hypoplastic optic nerve,malformation of outflow system. Caused by mutation of pax-6 gene.

Human Gene
SOX2 CHX10 PAX6

Associated Disease(s)

Anophthalmia Microphthalmia, cataracts & iris abnormalities Aniridia, Peters anomaly, anterior segment dysgenesis, foveal hypoplasia, autosomal dominant keratitis, congenital cataract Renal-coloboma syndrome Axenfeld-Rieger syndrome, iridogoniodysgenesis, Peters anomaly Anterior segment mesenchymal dysgenesis & cataracts, congenital cataracts Anterior segment dysgenesis Lymphedema-distichiasis, familial distichiasis Blepharophimosis syndrome Congenital fibrosis of extraocular muscles, type 2 Cone-rod dystrophy 2; Leber congenital amaurosis; retinitis pigmentosa

PAX2 PITX2 PITX3 FOXC1 FOXC2 FOXL2 ARIX CRX

FROM SURFACE ECTODERM Lens; lacrimal gland; epithelium of cornea; conjunctiva and adnexal glands and epidermis of eyelids. FROM NEURAL CREST Corneal keratocytes; endothelium of the cornea; trabecular mesh work; stroma of iris and choroid; ciliary muscle and optic nerve meninges. FROM NEURAL ECTODERM Retina and retinal pigment epithelium; pigmented and non pigmented layers of ciliary Epithelium; dilator and sphincter muscles of iris.