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Embryology of Eye

anatomical consideration of development of eye from embryonic stage. gives insight into future anatomical and pharmacological basis of drug development in disorders of eye.

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Embryology of Eye

  2. 2. Netra Uthpathi  It is gyanendriya adhisthanm meant for rupa grahanam.  Indriyas derived from atma.  Perticularly from vaikarik and taijas ahankar –all the 11 indriyas develop.(Su)  Netra indriya derived from Agni mahabhuta(Su)  Satwaguna+RajaGuna+Agnimahabhuta=Chaksyu indriya(A.H)  According to A.S-Drusti is formed by essence of Kapha, Raktha and and pancha mahabhutas. Sukla mandalam- by the essence of kapha(Pittrija) Krishna mandalam-By Raktha(Matrija) Drustimandal- By both
  3. 3.  Drusti is formed by the essence of Pancha mahabhutas with Agni mahabhuta predominance.(Su) Mamsa- Pruthwi mahabhuta Raktha-Agni Krishna mandala-Vayu Sweta Mandala- Jala Ashru Margam-Akasha mahabhuta.  According to Bhela - Aochak pitta takes part in perception of vision, is of two types- Budhi vaisesik and Chaksyu vaisesik.
  4. 4. INTRODUCTION  Ocular development is a continuous process and does not proceed in a discrete stages.  For better understanding and description , the process of ocular development is divided into 3 stages: Embryogenesis Organogenesis Differentiation.  Embryogenesis- Formation of three germinal layers of the developing fetus-ectoderm, mesoderm and endoderm.  Organogenesis- Segregation and arrangement of the primitive tissues to form the general pattern of the organ,result in the development of the framework of eye.  Differentiation-The specific components of the eye are developed
  5. 5. EMBRYOGENESIS Morula Epiblast EndodermMesoderm Hypoblast Ectoderm Blastocyst Embryoblast
  6. 6. cont. Cephalad ectoderm Neural ectoderm Neural plate Neural fold And Neural tube Prosencephalon Anterior neural fold Brain Two Lateral neural folds Optic pit or Optic sulcus
  7. 7. Derivatives of embryonic tissues
  8. 8. ORGANOGENESIS Starts by 3rd week of gestation. The first evidence of primitive eye formation occurs during this period. Neural Plate Procencephalon Optic sulcus or optic pit(thickened and depressed area on either side ). As the optic sulcus deepens, the wall of the procencephalon overlaying the sulcus bulges outwards to form the optic vesicle.  The proximal part of optic vesicle constricted and elongated to form optic stalk.
  9. 9. FORMATION OF THE LENS  Development of lens can be divided into two phases: 1.development of lens vesicle and 2. development of lens fibers. DEVELOPMENT OF LENS VESICLE  Optic vesicle grows laterally and comes in contact with surface ectoderm.  Between 24th to 26th day, the surface ectoderm adjacent to the optic vesicle thickens to form the lens placode.  The lens placode invaginates to form the lens vesicle(between 32nd to 33rd day), which has a hallow center.  After the lens vesicle separated from the surface ectoderm, it is surrounded by basal lamina, which becomes lens capsule.  Cuboidal cells line the anterior part of the lens vesicle and the posterior portion of the lens vesicle is lined by columnar cells that form the primary lens fiber.
  10. 10. Optic vesicles: dilated end of diverticulum- invaginates & sinks below the surface ectoderm to form double layered optic cup. Lens placode  lens vesicle. By 22 days of conception, optic peduncles: a bilateral evagination of the neuroectoderm of the forebrain. By 27 days, optic vesicles (hollow balls of neuroectoderm connected to the brain- 3rd ventricle- through the hollow optic stalk) reach surface ectoderm and induce formation of lens placode.
  11. 11. Formation of lens vesicle and optic cup.
  12. 12. DEVELOPMENT OF LENS FIBER  The cells of anterior wall do not devide and forms the lens epithelium.  The posterior culumnar cells do not devide but elongates to form primary lens fibers and obliterate the lumen of the vesicle.  The primary lens fiber occupy the central portion of the lens forming the embryonic nucleus.  This occurs between 5th to 8th week of gestation.
  13. 13. Cont..  The primary lens fibers become attached to the apical surface of the anterior lens epithelium.  Nuclei of the lens fibers move anteriorly within the cells to form a line convex forward  neuclear bow.  Secondary lens fibers  additional lens fibers that are formed by the division of the anterior epithelial cells of the equator.  New secondary lens fibers will be formed throughout life and lens keeps enlarging.  At their anterior end(basal end) the fibers remain attached to the basal lamina while their apical ends extend around the primary fibers beneath the capsule.  The length of fibers not enough to reach from the anterior to the posterior pole. At the two surfaces of the lens, therefore the ends of the lens fibers meet one another successively to form lens sutures.(2nd to 4th month)  The anterior becomes “Y” shaped and the posterior becomes inverted “Y” shaped.
  14. 14. Cont.. Structure of the crystalline lens Y-shaped sutures of the fetal nuclear fibres
  15. 15. Cont..  The lens continues to grow through out the life through the proliferation of secondary fibers  Due to the various stages of differentiation and different optican dencities the lens nuclei produce 4 zones 1. The embryonic nucleus-an optically clear central area formed in embryonic life(during 1st to 3rd month) from primary lens fibers , which retains embryonic transparency. 2. The fetal nucleus-formed from secondary fibers from the 3rd to 8th month of fetal life. 3. The infantile nucleus- formed from the last week of fetal life through puberty. 4. The adult nucleus-formed after puberty in adult life.
  16. 16. DEVELOPMENT OF CORNEA  Cornea: develops from surface ectoderm and mesoderm  At 5 to 6 weeks of gestation-the surface ectoderm separates the lens vesicle to form the corneal epithelium.  7 weeks- mesenchyma cells derived from neural crest cells migrate forward from around lens vesicle 3 waves.  The first wave of cells- trabecular endothelium  The 2nd wave of cells – corneal stroma  The 3rd wave of cells – migrate between the corneal endothelim and lens to form- the iris stroma.  The final adult corneal epithelium attained by 37 weeks.  The corneal endothelium forms a two cell layer of cuboidal cells.In 8th week the cells produce a basement membrane- Decement’s membrane.  8 to 9 weeks- basal lamina of epithelim-produce Bowman’s membrane.  SCLERA: derived from neural crest .Condensation of neural crest tissue unitl12th week of development , sclera surrounds the optiv nerve.
  17. 17. FORMATION OF THE OPTIC CUP AND CHOROIDAL FISSURE  During 4th week of gestation, the optic vesicle is converted into a double layered optic cup. This happens simultaneously while the lens vesicle is being formed.  The margin of optic cup grows over the upper and lateral surface of the lens to enclose it except in the inferior part of the lens.  The inferior invagination of the optic vesicle extends proximally to involve the optic stalk. A deep groove appears on the ventral surface of the growing optic cup and stalk, which is known as choroidal , embryonic or fetal fissure.  The embryonic fissure is essential for the growth and development of the eye since it allows the exit of axons from ganglion cells forming the optic nerve and the entry of the vascular system to nourish the developing eye.  Vascular mesenchyme: grows inside the optic fissure taking hyaloids artery with them. By 33 days.  Embryonic fissure closer around 33rd day. • Optic canal: a narrow tube inside the optic stalk formed by 7th week by narrowing & closure of optic fissure margins around the artery. Failure coloboma
  18. 18. DEVELOPMENT OF RETINA  Retina consists of two layers developed from optic cup: pigmented layer and neural layer and inter-retinal space (lumen) between them that is continuous through the optic stalk with the 3rd ventricle.  The retina develops from the two parts of the optic cup 1. Outer layer of the optic cup- RPL(6th week) 2. Inner layer of optic cup- Neurosensory retina(6th wks-22nd wks )  6th weeek- outer wall of optic cup- become pigmented-posterior part forms the RPL and anterior part continues forward in the cilliary body and iris as their pigment epithelium.  Neural retina initially consists of 1. Outer neural epithelium- filled with 8 to 9 rows of nuclei 2. Inner marginal zone-devoid of nuclei called as the layer of His  Neural epithelium differentiated into two layers the inner and outer neuroblastic layers and the transient layer of Chievitz, which subsequently disapears.  The inner neuroblastic layer differentiates to form- ganglion cells, Muller cells and amacrine cells(inner plexiform layers)  The outer neuroblstic layer differentiates to form- rods and cones, bipolar cells and horizontal cells(outer plexiform layer)
  19. 19. DEVELOPMENT OF MACULAAND OPTIC NERVE  Development of macula delayed upto 8 months of gestation.  Thickening of ganglion cell layer temporal to the disc- 5th month.  6th month-center of macula-8 rows of nuclei.  Outer nuclear layer with immature cones , to the periphery immature rods.  7th month-foveal depression starts.  4th month after birth-Both the ganglion cell layer and inner nuclear layer retreat to the foveal slopes, leaving the cone nuclei bare in the center of the depression.  Optic stalk develops into optic nerve.The optic stalk forms a connection between the primary optic vesicle and the fore brain.  Optic fissure closure-5th week- optic stalk becomes a tube –receive axons of ganglion cells and nerve fibes.  The epithelial cells of the inner wall of the stalk forms the glial system of optic nerve.The outer basal lamina forms –glial lamina cribrosa.  Latter with disappearance of the hyloid system, the pappila also atrophies leaving a physiological cup.  The optic nerve sheath are derived from neural crest mesenchyme.
  20. 20. DEVELOPMENT OF UVEAL TRACT  Developed from the mesoderm and partly from the neuroectoderm.  Choroid -From mesenchyme surrounding the optic vesicle with contribution of cranial neural crest cells.  1 to 2 month s- capillary channels , primitive choroid  3 months- chorio capillary forms from posterior to anterior.  6 to 7 months- Uveal melaniasation starts at disc and continues after birth.(RPE melanization 5th week)  Bruch’s membrane is formed from outer layer of the optic cup.  Ciliary body – (3rd month) from both neuroectoderm and mesoderm.  Two layered optic cup extends towards lens- pars caeca and pars optica, the junction of these two is Orra serrata.  Ciliar muscle- 4th month- from mesoderm  Iris – 3rd month- forward extension of both wall of optic cup.  Vascular mesenchymae from neural crest forms-iris stroma.  The anterior part of tunica vasculosa lentis is replaced by the pupillary membrane.  The spinchter and dilator muscles are neuroectodermal in origin.  Mature melanosomes are found in the iris around9 months of gestation.
  21. 21. VITVREOUS DEVELOPMENT  3 FOLD ORIGIN  Primary(primitive) -6 weeks (13 mm stage)-cellular. Partly mesodermal and partly surface ectodermal. Later the hyloid system of blood vessel invades through the embryonic fissure.  Secondary(Definitive)- 8 weeks(60-70mm)the neuroectoderm of optic vesicle forms the secondary vitreous. (Vascular, hyloid vessels, collagen fibrils,hyaluronic acid)  Arises between the primitive vitreous + retina and develops from the retina.  Starts as a homogenous gel that increases in volume rapidly & pushes the primitive vitreous anteriorly to behind the lens.  Hyalocytes  derived from mesenchyme around hyaloids vessels. Migrates into definitive vitreous.Later hyaloids vessels atrophy & disappear leaving the acellular hyaloids canal.  Tertiary vitreous-> 12 weeks.The cilliary zonules are derived from the neuroectoderm of cilliary region forms the tertiary vitreous. Represented by vitreous base and cilliary zonules.  If the regression of primary vitreous fails –PHPV( Persistent Hyperplastic Primary Vitreous)
  22. 22. DEVELOPMENT OF EYE LID , CONJUCTIVA AND NASOLACRYMAL DUCT  1st sign of eye lid development- lid fold starts by 7th week.  Eye lid from both surface ectoderm and mesenchyme.  Tarsus- from condensation of mesenchymal tissue.  Upper lid from lateral and medial frontonasal process of mesenchymal condensation.  Lower lid from maxillary process.  Fusion of two lid around 9th week  Inward migration of ectodermal tissue gives rise to meibomian glands, sweat glands and cillia.  Failure of fusion gives rise to coloboma of lids  Lids finally starts separating by 5th to 7th month.  Incomplete separation- Ankyloblepharon  Final maturation starts by 7th month of gestation.
  23. 23.  Conjunctival sac  formed in front of cornea while eyelids are fused.  Connective tissue + tarsal plates  formed from mesenchyme core of eyelids  Orbicularis oculi muscle  formed from mesenchyme of second pharyngeal arch which invades the eyelids & supplied by 7th cranial nerve.  Ciliary glands (moll & zeis)  grow out from ciliary follicles  Tarsal glands (meibomian glands)  develop as columns of ectodermal cells from the lid margin  Lacrimal glands  form as a series of ectodermal buds that grow seperatly from the superior fornix at the conjunctiva into the underlying mesenchyme  The buds later unite  form secretory units & multiple ducts of the gland  After development of levator palpbrae superioris  gland is divided into orbital & palpebral  Tears are produced 3rd month after birth  Lacrimal sac & Nasolacrimal duct:  Solid cord at ectodermal cells between the lateral nasal process & maxillary process of the face.  Cord is canalized to form the nasolacrimal duct. Superior end dilates to form lacrimal sac.  Lacrimal duct formed by cellular proliferation.
  24. 24. SUMMARY OF OCULAR EMBROYOGENESIS PERIOD AFTER CONCEPTION MAJOR MILESTONE 3 weeks Optic groove appears 4 weeks Optic pit develops into optic vesicle Lens plate/placode forms Embryonic fissure develops 1st month Lens vesicle forms Hyaloid vessel develops 1 ½ month (6 weeks) Closer of embryonic fissure Differentiation of RPE Proliferation of neural retinal cells Appearance of eye lid folds and nasolacrimal ducts 7th week Formation of embryonic nucleus of lens, sclera bigins to form, Migration of waves of neural crest to form corneal endothium, stroma and iris stroma. 3rd month Rod and cones precussor differentation , anterior chamber appears, Fetal nucleus stats to develop
  25. 25. 4th month Hyaloid vessel begins to regress, Formation of physiological optic disc cup. Bowmans membrane appears. 5th month Eye lid separation begins 6th month Differentiation of dilator pupillae muscle, cones differentiate, Naso lacrimal system becomes patent. 7th month Rods differentiate, Myelination of optic nerve, retinal vessels starts reaching nasal periphery 8th month Hyaloid vessel dissapears 9th month Pupillary membrane dissapears After birth Macular region develops further.
  26. 26. Part Derived from Lens Surface ectoderm Retina Neuroectoderm (optic cup) Vitreous Mesoderm- mesenchyme Choroid Mesoderm (infiltrated by neural crest cells) Ciliary body Mesoderm Ciliary muscles Mesenchymal cells covering the developing ciliary body (neural crest) Iris Mesoderm- mesenchyme Muscles of the iris Neuroectoderm (from optic cup) Sclera Mesoderm (infiltrated by neural crest cells?) Cornea Surface epithelium by ectoderm, substantia propria and inner epithelium by neural crest Conjunctiva Surface ectoderm Blood vessels mesoderm- mesenchyme Optic nerve Neuroectoderm. Its covering (pia, arachnoid and dura) are derived from mesoderm SUMMERY OF DEVELOPMENT OF EYE BALL
  27. 27. DEVLOPMENTAL OCULAR ANOMALIES  Anophthalmia- congenital absence of eye- optic pit does not develop properly  Microphthalmia  Congenital cystic eye- arrest of inavination of optic vesicle to form optic cup.  Cyclopia – total fusion of the optic vesicles.  Synophthalmia- partial fusion of the optic vesicle.  Colobomas : coloboma refers to any notch, gap or fissure. Coloboma occurilure of closer of embryonic fissure. May be iris, choroid ciliary body, retina, and optic nerve.  Lens abnormalities:  Congenital Aphakia- lens failed to develop.  Microspherophakia- bilateral , small and spheric lens.  Anterior lenticonus, posterior lenticonus and developmental cataract.  Persistent pupilary membrane and Metendorf’s dot – due to failure of regression of Hyloid system of vessels. ( third month).
  28. 28.  SCLERAL ANOMALIES- Blue sclera- blue clera, brittle bone and deafness triad in osteogenesis imperfecta  CORNEAL ANOMALIES  SCLEROCORNEA- limbus is clinically indiscnict and the opque scleral tissue extend to the cornea.  Microcornea- <11mm  Megalocornea- >14mm  Posterior keratoconus  Posterior embryotoxon- white line on the cornea with strands of iris from peripheral iris to this white line.  Axenfeld - Rieger syndrome  Peters’ anomaly– central corneal opacity that persists fron birth- due to failure or incomplete separation of lens vesicle from the surface ectoderm.  Anomalies of Iris: corectopia, Aniridia  Vitreous anomalies-PHPV
  29. 29. Cont..  OPTIC NERVE Anomalies: Optic nerve apasia, optic nerve hypoplasia,  Morning Glory Disc Anomaly-  Lid Anomaleis- Cryptophthalmos –sheet of the skin covers the eye- due to failure of separation of the lids during 5th months of gestation.  Eye lid colobomas  Congenital ptosis  Ankyloblepharon  RETINAL – Retinal dysplasia.
  30. 30. CYCLOPIA  Complete fusion of optic vesicles
  39. 39. REFERENCES  Text book of ophthalmology- Agarwal and co-Jaypee publication  Chapter 53. Ocular Developmental Anomalies SCOTT E. OLITSKY and LEONARD B. NELSON.  Comprehenive ophthalmology-A K Khurana-5th edition.  Post graduate ophthalmology- Choudhuri and M. Vanitha  Modern ophthalmology- L.C.Dutta.  Parsons’ Diseases of Eye-21st edition.  Shalakaya Tantra –Dingari Laxman Chari-first edition-2005.