EMBRYOLOGY presentation for group one final copy

Detailed embryology

1. EMBRYOLOGY 1 DEVELOPMENT OF THE EYE AND ITS STRUCTURES GROUP 1 LERIONKA ALBERT RATUMO CAROLINE SCARLET MACHUNA DEONICIA NDAMBUKI LANGAT JULIUS

2. Main objective To understand the origin and developmental processes of human eye and its related structures .

3. REGULATION OF EYE DEVELOPMENT Development of the eye involves: -Interaction of cells -Movement of cells from distant regions of the embryo The primary tissues involved are the epidermis, neuroectoderm and mesenchyme

4. Factors associated with eye development Growth factors Homeobox factors Neural crest cells

5. Growth factors They are signaling molecules that regulate cell proliferation, differentiation, and migration during eye development. They include: 1: Fibroblast growth factor : used in induction of the optic cup, lens formation, and retinal differentiation. 2: Transforming growth factor beta : important for corneal development and regulation of extracellular matrix component during eye development. 3: Insulin growth factor : differentiation of lens epithelial cells immediately anterior to the equator—as well as their mitotic activity .

6. Homeobox genes Are group of trascription factors that regulate the spatial and temporal expression of other genes during eye development. They include: 1: PAX 6> master gene in eye development, its crucial for the formation of lens, cornea and retina. Mutation of this gene can lead to severe eye defects such as, aniridia or anophthalmia 2: Sonic hedgehog gene : essential for separation of the single optic field into two distinct eyes. Also patterning of the optic stalk and retinal ganglion cells. 3: HOX (HOX8 and HOX 7): for corneal epithelium and ciliary body formation respectively.

7. Neural crest cells Are migratory population of cells that originate from neural tube and contribute to the development of various eye structures particularly those outside the retina like the cornea, iris, ciliary body,sclera and the optic nerve sheath.

8. Week 3-Week 8 Optic pits develop from optic sulci Neural crest cells begin to migrate Neural tube closes and it flexes ventrally

9. Week 3-week 8 ct …

10. Development of the eye Eyes are derived from four sources 1: Neuroectoderm of the forebrain Retina, posterior layers of the iris and optic nerve 2: Surface ectoderm of the head Lens and corneal epithelium 3: Mesoderm between the above layers Fibrous and vascular coats 4: Neural crest cells Choroid,sclera and corneal endothelium.

11. Overview of the eye structures 1: Fibrous coat a. sclera -give shape to the eyeball and protects , b . cornea -focus light, protects structures inside the eye 2.: Vascular pigmented coat a. Iris –let light into the eye b. ciliary body- shape the lens when the eye focuses c. Choroid – filled with blood vessels that nourishes the eye. 3: Nervous coat a .retina - turn light to electrical signals i . pigmented layer ii. nervous layer a- Optica retinae (post 4/5-photoreceptive layer b- caeca retinae (ant 1/5)- pars iridicae - pars ciliaris

12. Eye development ct ….. Eye development is first evident at the beginning of the 4th week. Optic grooves appear in the neural folds at the cranial end of the embryo optic grooves evaginate to form hollow diverticula-optic vesicles -that project from the wall of the forebrain into the adjacent mesenchyme the distal ends of optic vesicles expand and their connections with the forebrain constrict to form hollow optic stalks

13. The optic vesicles soon come in contact with the surface ectoderm which thickens to form lens placodes which subsequently invaginate forming lens pits that develops into lens vesicles During the 5th week , the lens vesicle loses contact with the surface ectoderm and lies in the mouth of the optic cup As they are developing, the optic vesicles invaginate to form double-walled optic cups Linear grooves- retinal fissures (optic fissures)-develop on the ventral surface of the optic cups and along the optic stalks Formation of this fissure allows the hyaloid artery to reach the inner chamber of the eye. During the 7th week , the lips of the choroid fissure fuse, and the mouth of the optic cup becomes a round opening, the future pupil .

14. developing lens influence the inner layer of the optic cup to proliferates and form a thick neuroepithelium . the cells of this layer differentiate into the neural retina , the light-sensitive region of the optic part of the retina ( contains photoreceptors ( rods and cones ) and the cell bodies of neurons (e.g., bipolar and ganglion cells ). The axons of ganglion cells in the superficial layer of the neural retina grow proximally in the wall of the optic stalk to the brain. As a result, the cavity of the optic stalk is gradually obliterated as the axons of the many ganglion cells form the optic nerve

15. The fissures contain vascular mesenchyme from which the hyaloid blood vessels develop. The hyaloid artery , a branch of the ophthalmic artery , supplies the inner layer of the optic cup, the lens vesicle, and the mesenchyme in the cavity of the optic cup. The hyaloid vein returns blood from these structures. As the edges of the retinal fissure fuse, the hyaloid vessels are enclosed within the primordial optic nerve. Distal parts of the hyaloid vessels eventually degenerate, but proximal parts persist as the central artery and vein of the retina .

16. Ventrolateral view of the optic cup and optic stalk of a 6-week embryo. The choroid fissure on the undersurface of the optic stalk gradually tapers off.

17. Development of the Retina The retina develops from the walls of the optic cup, an outgrowth of the forebrain. The outer, thinner layer of the optic cup becomes the retinal pigment epithelium (pigmented layer of retina-characterized by small pigment granules) The inner, thicker layer differentiates into the neural retina (neural layer of retina). During the embryonic and early fetal periods, the two retinal layers are separated by an intraretinal space

18. Development of the inner (neural) layer of the optic cup The posterior four-fifths , the pars Optica retinae , contains cells bordering the intraretinal space that differentiate into light-receptive elements, rods and cones. Adjacent to this photoreceptive layer is the mantle layer , which, as in the brain, gives rise to neurons and supporting cells, including the outer nuclear layer, inner nuclear layer, and ganglion cell layer. On the surface is a fibrous layer that contains axons of nerve cells of the deeper layers. Nerve fibers in this zone converge toward the optic stalk, which develops into the optic nerve

19. Continuation……. The anterior fifth of the inner layer , the pars ceca retinae, remains one cell layer thick. It later divides into the; 1: pars iridica retinae- which forms the inner layer of the iris 2: pars ciliaris retinae - which participates in formation of the ciliary body

20. Various layers of the pars Optica retinae(post 4/5) in a fetus of approximately 25 weeks

21. Development of the Iris develops from the rim of the optic cup , which grows inward and partially covers the lens The epithelium of the iris represents both layers of the optic cup it is continuous with the double-layered epithelium of the ciliary body and with the retinal pigment epithelium and neural retina. The connective tissue framework ( stroma) of the iris is derived from neural crest cells that migrate into the iris. The dilator pupillae and sphincter pupillae muscles of the iris are derived from neuroectoderm of the optic cup.

22. Cont … .. Region between the optic cup and the overlying surface epithelium is filled with loose mesenchyme where the sphincter and dilator pupillae muscles that originate from ectoderm. In the adult, the iris is formed by; 1. the pigment-containing external layer , 2. the unpigmented internal layer of the optic cup 3. a layer of richly vascularized connective tissue that contains the pupillary muscles

23. Development of the Ciliary Body is a wedge-shaped extension of the choroid . Its medial surface projects toward the lens, forming ciliary processes . The pigmented portion of the ciliary epithelium is derived from the outer layer of the optic cup and is continuous with the retinal pigment epithelium . The nonpigmented portion of the ciliary epithelium represents the anterior prolongation of the neural retina in which no neural elements develop. The ciliary muscle (change lens shape when focusing near object) and the connective tissue in the ciliary body develop from mesenchyme located at the edge of the optic cup in the region between the anterior scleral condensation and the ciliary pigment epithelium.

24. … Cont … The pars ciliaris retinae is easily recognized by its marked folding. Externally, it is covered by a layer of mesenchyme that forms the ciliary muscle; on the inside, it is connected to the lens by a network of elastic fibers, the suspensory ligament or zonula . Contraction of the ciliary muscle changes tension in the ligament and controls curvature of the lens.

25. Development of the iris and ciliary body. The rim of the optic cup is covered by mesenchyme, in which the sphincter and dilator pupillae develop from the underlying ectoderm

26. Development of the Lens After formation of the lens vesicle , cells of the posterior wall begin to elongate anteriorly and form long fibers that gradually fill the lumen of the vesicle. By the end of the seventh week , these primary lens fibers reach the anterior wall of the lens vesicle. Growth of the lens is not finished at this stage, however, since new ( secondary) lens fibers are continuously added to the central core.

27. Choroid, Sclera and Cornea End of the fifth week , the eye primordium is completely surrounded by loose mesenchyme. This tissue soon differentiates into; 1: an inner layer comparable with the pia mater- this layer later forms a highly vascularized pigmented layer known as the choroid (fill with blood vessels that bring oxygen and nutrients to the eye) 2: an outer layer comparable with the dura mater- this layer develops into the sclera (maintain eyeball shape and protects from injury) and is continuous with the dura mater around the optic nerve Sclera is covered by conjunctiva that moisturize the eye

28. Differentiation of mesenchymal layers overlying the anterior aspect of the eye The anterior chamber forms through vacuolization and splits the mesenchyme into; 1: an inner layer in front of the lens and iris, the iridopupillary membrane , 2:an outer layer continuous with the sclera, the substantia propria of the cornea. The anterior chamber itself is lined by flattened mesenchymal cells

29. Development of the cornea The cornea is formed by; 1: an epithelial layer derived from the surface ectoderm, 2 : the substantia propria or stroma , which is continuous with the sclera, 3: an endothelial layer , which borders the anterior chamber .

30. Cont ….. The iridopupillary membrane in front of the lens disappears completely. The posterior chamber is the space between the iris anteriorly and the lens and ciliary body posteriorly . The anterior and posterior chambers communicate with each other through the pupil and are filled with fluid called the aqueous humor produced by the ciliary process of the ciliary body. Non pigmented layer.

31. Cont … . The clear aqueous humor circulates from the posterior chamber into the anterior chamber providing nutrients for the avascular cornea and lens . From the anterior chamber, the fluid passes through the scleral venous sinus (canal of Schlemm ) at the iridocorneal angle where it is resorbed into the bloodstream. Via scleral veins. NB- Blockage of the flow of fluid at the canal of Schlemm is one cause of glaucoma.

32. Development of the Vitreous Body Mesenchyme surrounds the eye primordium from the outside and also invades the inside of the optic cup by way of the choroid fissure. Here, it forms the hyaloid vessels, which during intrauterine life supply the lens and form the vascular layer on the inner surface of the retina. It also forms a delicate 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.

33. Section through the eye of a 15-week fetus showing the anterior chamber, iridopupillary membrane, inner and outer vascular layers, choroid, and sclera.

34. Eyelids Development Eyelids are formed by reduplication of surface ectoderm above and below the cornea The folds enlarge and their margins meet and fuse with each other. The lids cut off a space called the conjunctival sac . The folds thus formed contain some mesoderm which would form the muscles of the lid and the tarsal plate . The lids separate after the seventh month of intrauterine life . Tarsal glands are formed by ingrowth of a regular row of solid columns of ectodermal cells from the lid margins. Cilia develop as epithelial buds from lid margins

35. Development of the conjunctiva Conjunctiva develops from the ectoderm lining the lids and covering the globe . Conjunctival glands develop as growth of the basal cells of upper conjunctival fornix. Fewer glands develop from the lower fornix.

36. Development of the lacrimal apparatus Lacrimal gland develops from about 8 cuneiform epithelial buds which grow by the end of 2 nd month of fetal life from the superolateral side of the conjunctival sac. Lacrimal sac, nasolacrimal duct and canaliculi develop from the ectoderm of nasolacrimal furrow which extends from the medial angle of eye to the region of developing mouth. The ectoderm gets buried to form a solid cord which is later canalized. The upper part forms the lacrimal sac.

37. The nasolacrimal duct is derived from the lower part as it forms a secondary connection with the nasal cavity. The ectodermal buds arise from the medial margins of eyelids which are later canalized to form the canaliculi.

38. Extraocular muscles development All the extraocular muscles develop in a closely associated manner by mesodermally derived mesenchymal condensation . This probably corresponds to preotic myotomes , hence the triple nerve supply (III, IV and VI cranial nerves).

39. Structures Derived from the Embryonic Layers 1. Surface ectoderm • The crystalline lens • Epithelium of the cornea • Epithelium of the conjunctiva • Lacrimal gland • Epithelium of eyelids and its derivatives viz., cilia, tarsal glands and conjunctival glands • Epithelium lining the lacrimal apparatus

40. 2. Neural ectoderm • Retina with its pigment epithelium • Epithelial layers of ciliary body • Epithelial layers of iris • Sphincter and dilator pupillae muscles • Optic nerve (neuroglia and nervous elements only) • Melanocytes • Secondary vitreous • Ciliary zonules (tertiary vitreous).

41. 3: Associated paraxial mesenchyme • Blood vessels of choroid, iris, ciliary vessels, central retinal artery, other vessels • Primary vitreous • Substantia propria, Descemet’s membrane and endothelium of cornea • The sclera • Stroma of iris • Ciliary muscle Sheaths of optic nerve • Extraocular muscles

42. • Fat, ligaments and other connective tissue and structures of the orbit. Upper and medial walls of the orbit • Connective tissue of the upper eyelid structures of the orbit

43. Chronology of Embryonic and Fetal Development of the Eye 22 days : Optic primordium appears in neural folds (1.5-3.0 mm). 25 days : Optic vesicle evaginates. Neural crest cells migrate to surround vesicle. 28 days : Vesicle induces lens placode. Second month Invagination of optic and lens vesicles. Hyaloid artery fills embryonic fissure. Closure of embryonic fissure begins. Pigment granules appear in retinal pigment epithelium.

44. 2 nd month cont …. Primordia of lateral rectus and superior oblique muscles grow anteriorly. Eyelid folds appear. Retinal differentiation begins with nuclear and marginal zones. Migration of retinal cells begins. Neural crest cells of corneal endothelium migrate centrally. Corneal stroma follows. Cavity of lens vesicle is obliterated. Secondary vitreous surrounds hyaloid system. Choroidal vasculature develops. Axons from ganglion cells migrate to optic nerve. Glial laminal cribrosa forms. Bruch's membrane appears.

45. Third month Precursors of rods and cones differentiate Anterior rim of optic vesicle grows forward, and ciliary body starts to develop. Sclera condenses. Vortex veins pierce sclera. Eyelid folds meet and fuse .

46. Fourth month Retinal vessels grow into nerve fiber layer near optic disc. Folds of ciliary processes appear . Iris sphincter develops. Descemet's membrane forms. Schlemm's canal appears. Hyaloid system starts to regress. Glands and cilia develop. Fifth month Photoreceptors develop inner segments. Choroidal vessels form layers. Iris stroma is vascularized. Eyelids begin to separate.

47. Sixth month Ganglion cells thicken in macula. Recurrent arterial branches join the choroidal vessels. Dilator muscle of iris forms. Seventh month Outer segments of photoreceptors differentiate. Central fovea starts to thin. Fibrous lamina cribrosa forms. Choroidal melanocytes produce pigment. Circular muscle forms in ciliary body

48. Eighth month Chamber angle completes formation. Hyaloid system disappears. Ninth month Retinal vessels reach the periphery. Myelination of fibers of optic nerve is complete to lamina cribrosa. Pupillary membrane disappears.

49. Eye at birth Anteroposterior diameter of the eyeball is about 16.5 mm (70% of adult size which is attained by 7-8 years). Corneal diameter is about 10 mm. Adult size (11.7 mm) is attained by 2 years of age. • Anterior chamber is shallow and angle is narrow. • Pupil is small and does not dilate fully. • Lens is spherical at birth. Infantile nucleus is present. • Retina. Apart from macular area the retina is fully differentiated. Macula differentiates 4–6 months after birth. • Myelination of optic nerve fibres has reached the lamina cribrosa.

50. Cont ….. Refractive status. Newborn is usually hypermetropic by +2 to +3 D. • Orbit is more divergent (50°) as compared to adult (45°). • Lacrimal gland is still underdeveloped and tears are not secreted.

51. Postnatal period • Fixation starts developing in first month and completed in 6 months. • Macula is fully developed by 4–6 months. • Fusional reflexes, stereopsis and accommodation are well developed by 4–6 months. • Cornea attains normal adult diameter by 2 years of age. • Lens grows throughout life

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