Embryology of eye


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Embryology of eye

  1. 1. Embryology of Eye Varun Shrestha First Year Resident Nepal Eye Hospital 2013
  2. 2. Importance • To understand the structure of normal adult eye and its anatomic characteristics • the pathogenesis of numerous congenital anomalies of the eye that may occur as a result of defective embryogenesis • The various diseases of the eye
  3. 3. 3 elements have been identified that regulate: • Growth Factors  Fibroblast growth factors (FGF)  Transforming Growth Factor- (TGF Insulin like Growth factor-I (IGF-I) and TGF- ) • Homeobox genes - DNA sequence found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis)  PAX 6  HOX (HOX8.1, HOX 7.1) • Neural crest cells
  4. 4. Synergistic action of these multiple trophic factors appears to be a significant regulatory tool for • Initiating cellular activities and • For limiting abnormal development
  5. 5.  Neural plate Ectodermal cells of anterior portion of embryonic plate proliferates + thickens  Neural groove Medial longitudinal furrow  Neural fold Elevation at 2 sides of the neuroectoderm  Neural Tube neural folds meet at midline
  6. 6. At the anterior portion of the neural tube 3 dilatations are formed
  7. 7. The eye begins to develop as a pair of optic vesicles on each side of the forebrain Of the three germ layers of the embryo, only two are involved in the development of eye • Ectoderm – surface ectoderm neuroectoderm • Mesoderm
  8. 8. EMBRYOGENESIS OF EYE • PRIMITIVE EYE  starts in 3rd week of gestation when anterior portion of neural tube is closing. • It origins as optic pit thickening on either side of midline in the ventrolateral region of primitive forebrain
  9. 9. • The optic pit enlarges to form 2 globular structures at either side Primary Optic Vesicles. • Which connects to the forebrain via a n Optic Stalk • Primary optic vesicle meets surface ectoderm
  10. 10.  During 4th week of gestation optical vesicle invaginates distally and inferiorly  formation of two layered optic cup  Optic cup is widely open distally and inferiorly.  Invagination also involves the optic stalk so this inferior groove forms Optic fissure/ embryonic fissure
  11. 11. Invagination of optic vesicle Rim of optic cup Lateral wall of Forebrain Embryonic fissure
  12. 12. Embryonic fissure  Closes at 6th week  Closure begins at centre and extends anteriorly and posteriorly until only a small crescent remains open at the posterior pole.  IMPORTANCE: Through the fissure there is  Outgrowth of axons from ganglion cells which form the optic nerve  Ingrowth of vascular elements which aids in growth and development of the eye
  13. 13. Applied anatomy • Failure of fusion of this fissure -6th/7th week results in coloboma formation Anterior extreme  Colobomas of iris Posterior extreme  Colobomas of posterior fundus and optic nerve • Anterior and posterior aspects of cup are open for longer time hence it is exposed longer to teratogenic insults
  14. 14. Coloboma iris Coloboma optic disc
  15. 15. RETINA • Develop from two layers of optic cup  Sensory retina is formed by the Inner layer of optic cup  Retinal pigment epithelium is formed by the outer layer of optic cup
  16. 16.  Retinal Pigment layer It is a single layer of columnar cells  initially it is non-pigmented but at 5th week melanogenesis begins (Premelanosomesmelanosomes Differentiation begins at posterior pole and proceeds anteriorly  Neurosensory layer The anterior 1/5th  forms posterior surface of developing ciliary body and iris The posterior 4/5th  initially divided intoinner marginal zone -devoid of nuclei outer primitive nuclear zone which has 9 rows of nuclei
  17. 17.  Later the outer nuclear layer invades the inner marginal layer at the time of closure of embryonic fissure, so retinal Neurosensory cells divide into  Outer neuroblastic layer which contains horizontal, bipolar nerve cells, rod and cone cells  Inner neuroblastic layer which contains ganglion cells, amacrine cells, muller cells  These layers are separated by the Transient nerve fiber layer of Chievitz which later forms the inner plexiform layer  The inner 9 layers of retina are formed by merging of these two cell layers  By the 8th month of fetal life all layers of retina are recognizable
  18. 18. • Ganglionic cells are the first cell of retina to be clearly differentiated • Cones outer segment form - month • Outer Rods segment form -7 month • photoreceptor cells continue to form after birth so it develops the ability for increasing resolution and sensitivity
  19. 19. • Ora serrata – is a wavy line that lies between the small non nervous layer near the edge of cup large photosensitive portion in the inner layer of optic cup • Macula – has localized increase of superimposed nuclei in the ganglion cell layer, lateral to optic disc, in mid term • Fovea centralis – during 7th month, thinning of centre of macula due to peripheral displacement of ganglionic cells. Ganglionic layer Inner Nuclear layer Foveal Depression Outer plexiform layer/Henle’s layer *
  20. 20. Applied Anatomy  Areas where RPE does not form(sometimes along the line of closure) the underlying choroid/sclera/neuroretina is hypoplastic.  Retinal detachment- Potential space between the inner and outer layers of optic cup is the site for retinal detachment.  Foveal region is extremely thin, devoid of ganglion cells and retains relative transparancy, allowing persistent transmission of underlying highly vascular choroidal hue eg. Cherry Red spot (Sphingolipidoses)  Juvenile Retinoschisis- splitting of the retina in the nerve fiber layer.
  21. 21. OPTIC NERVE  Optic stalk and optic axons together form the optic nerve.  Its the constricted elongated area between primitive eye and forebrain  Initially there is an inner zone (neuroectodermal cells) and outer zone (undifferentiated neural crest)  th weeksome cells of inner region vacuolate+ degenerate+ remaining inner zone differentiates into glial cells.  Axons from ganglion cells run through the inner layer of stalk  Cells of inner layer encroach on the cavity of the stalk  cavity disappears  End of gestation Development of lamina cribrosa
  22. 22.  Myelination of axons of optic nerve begins just before birth and continues some time after birth  Optic disc- the point where the axons from ganglionic layer of retina converge to leave the posterior surface of optic cup along with the optic stalk  Optic chiasma- partial decussation of the axons of the 2 optic nerve  Optic tracts  Lateral geniculate bodies  Tectum of midbrain
  23. 23. • Applied anatomy: • Optic nerve – Aplasia – Hypoplasia • Morning Glory Syndrome - central excavation surrounded by an elevated rim of pink neuroglial tissue with the vessels emerging radially from the disc as spokes in all directions • Pit of the optic disc
  24. 24. Lens • Begins development at 3rd week • Derived from surface ectoderm • Triggered by interaction of forward growth of optic vesicle with surface ectoderm thickens and forms lens placode • It invaginates to form lens pit that eventually seperates + meets at the margin lens vesicle
  25. 25. CORNEAL EPITHELIUM ANTERIOR WALL- single layer of cuboidal epithelium POSTERIOR WALL- increases in length and form elongated fibres that projects into lumen of vesicle (crystallin) NUCLEAR BOW- nuclei of the lens fibers move anteriorly to form a convex line
  26. 26. • Nuclei disappears. • Additional lens fibers are formed by mitotic division of the anterior epithelial cells at preequatorial region Secondary fibers • These are formed through out life. • Basal ends are attached to the basal lamina while apical ends extends to primary fibers As the fibers are laid down concentrically laminar appearance of the lens • New fibres are added concentrically around the old central fibres around the equator
  27. 27. • Drawing shows formation of the lens vesicle and optic cup. The optic fissure is present because the optic cup is not fused inferiorly.
  28. 28. Different layers seen in adult eye: • Embryonic nucleus- 1st to 3rd month of embryonic life (Primary fibers) • Fetal nucleus- 3rd to 8th month of fetal life • Infantile nucleus- last weeks of fetal life to puberty • Adult nucleus- formed after puberty • Cortex- recently formed fibers, beneath epithelium anteriorly, beneath capsule posteriorly
  29. 29. • SUTURES  The linear juncture where the fibers terminate and abut each other. • Y Sutures- begin to form  2nd month  Anterior upright  Posterior inverted
  30. 30. • Later in gestation and following birth sutures become complex and dendriform. • LENS CAPSULE  Vascular lens capsule formed from mesenchyme surrounding the lens, Disappears after birth  True lens capsule formed from Thickened basal lamina, which develops from lens epithelium.
  31. 31. • The Zonular Apparatus begins to develop after the tertiary vitreous has formed. • Ciliary Epithelial cells synthesize collagen fibrils of the zonular fibers. • By 5th monthincrease in number, strength and merge with the anterior and posterior capsule.
  32. 32. Applied Anatomy  Unequal growth of fibers from posterior wall + New fibers growing from equatorial regions  Elliptical shape of lens  Lens epithelial cells left behind in the capsular bag after ECCE  PCO (posterior capsular opacification) development. Clinically 2 types of PCO, fibrosis type proliferation and migration of lens epithelial cells, which undergo Epithelial-to-Mesenchymal Transition fibrous metaplasia producing folds and wrinkles in the posterior capsule. pearl typeremnants located at the equatorial lens region (lens bow) causes regeneration of crystallin expressing lenticular fibers and forms Elschnig pearls and Soemmering ring  If sutures are not formed and the fibers meet at a single point at anterior and posterior pole a pit would be formed poor optical properties
  34. 34. THE VITREOUS BODY Develops between the lens and optic cup • Primary vitreous– formation at 1st month Network of delicate cytoplasmic processes derived partly from lens and partly from retinal layer of optic cup and mesenchymal cells Supplied by hyaloid vessels and its branches • Secondary vitreous - formation at 2nd month Between primary vitreous and retina and is avascular Derived from retina and replaces the primary vitreous extracellular matrix composed of type II collagen+ hyaloctes Hyaloid vessels undergo atrophy – hyaloid canal (5th -6th mth-) cloquet’s canal which extends from optic nerve head and posterior surface of lens, Funnel shaped
  35. 35. • Tertiary vitreous- at 4th month • Between ciliary processes and lens capsule • Large no. of collagen fibres develop with formation of zonular fibres
  36. 36. • Applied anatomy • Mittendorf’s dot: remnants of anterior end of hyaloid artery associated with posterior polar cataract & attached to posterior lens capsule. • Subluxation/Ectopia lentis: Partial or total failure in Tertiary vitreous development • Bergmelster’s Papillae: flakes of glial tissue projecting from the optic disc • Persistent Primary hyperplastic vitreous: U/L, premature child.
  37. 37. UVEA • • • • Middle vascular layer of eyeball Composed of iris, ciliary body choroid Stroma of all these are mesodermally derived Consists of blood vessels, pigmented cells called melanocytes and connective tissue.
  38. 38. IRIS  Developed from 2 layers  Mesoderm – Anterior stroma  Neuroectoderm-  iris pigment epithelium  sphincter and dilator muscles  pupillary membrane is formed by condensation of mesenchyme situated in the anterior surface of the lens  2 layers of neuroectoderm forming the edge of optic cup extend to the posterior surface of pupillary membranethese structures fuse to become iris  Opening in the central part of iris becomes the pupil  Pupillary membrane begins to degenerate at about 8th months of gestation
  39. 39.  Applied anatomy  Varying amount of atrophy of stromal vessels (pupillary membrane) while peripheral membrane remains well developed produce the fine architecture of iris crypts  Pigmentation of stroma doesn’t become evident until after birth, hence newborns usually have blue iris
  40. 40. Polycoria, Ectopia, Corectopia, Aniridia
  41. 41. CILIARY BODY AND SUSPENSORY LIGAMENTS OF LENS  Mesenchyme at edge of optic cup forms the Connective tissue of ciliary body,  Smooth muscle fibres of ciliary muscle,  suspensory ligaments of lens  2 epithelial layers formed from neuroectoderm at the edge of optic cup  outer pigmented  Inner devoid of pigment  Ciliary body is situated between future iris epithelium and peripheral retina  Ciliary epithelium undergoes folding to form 70-75 ciliary processes
  42. 42.  CHOROID Middle vascular coat of eyeball. Begins to form at the anterior region of the cup & proceeds posteriorly. Formed from mesenchyme surrounding the optic vesicle Has layers. The innermost Bruch’s membrane is derived from basement membrane of RPE , choriocapillaries layer, Elastic tissue and collagen fibrils The outer layers layers are the - vascular and capillary During 5th month melanocytes of neural crest origin may be seen Melanocytes of neural crest origin are predisposed to development of malignant melanoma
  43. 43. NUTSHELL:  Iris muscle-ectodermal in origin  Ciliary muscle is mesodermal in origin
  44. 44. CORNEA Formation of cornea is induced by lens and optic vesicle formation  Epithelium derived from – surface ectoderm  Bowman’s membrane and Substantia propria – mesenchyme  Descemet’s membrane – endothelial cells  Endothelium – neural crest
  45. 45. Keratoconus • Is a condition when the cornea assumes a conical shape secondary to stromal thinning
  46. 46. SCLERA  Outer tough fibrous coat of eyeball  Originates as the condensation of mesenchyme outside the optic cup  7th week of gestation  First forms at the limbal region and progresses peripherally until posterior pole is reached 5th month  Primitive mesoderm differentiates into collagen and elastic fibres of an adult sclera
  47. 47. ANOMALIES MICROCORNEA • Adult cornea<10mm in horizontal diameter • Related to fetal arrest of growth of cornea in 5th month MEGALOCORNEA • diameter 12mm or > at birth&13mm or>after 2 yrs • Due to failure of optic cup to grow &of its anterior tips to close
  48. 48. Sclerocornea • There is ‘sclera-like’ clouding of cornea • Disorder of second wave mesenchyme migration • 90% bilateral
  49. 49. ANTERIOR CHAMBER  It arises as a slit in the mesenchyme between the surface ectoderm and developing Iris.  th week angle of the anterior chamber is occupied by mesenchymal cells of neural crest originTrabecular meshwork  rd monthSchlemm’s canal develops from small plexus of venous canaliculi. The endothelial lining of Schlemm's canal is mesodermal in origin.  th monthVacuolation of the endothelium around Schlemm's canal occurs individual cells are connected by zonulae adherentes  Final differentiation of definitive filtration apparatus occurs shortly before birth.
  50. 50. Schlemm canal Trabecular meshwork Scleral spur
  51. 51. POSTERIOR CHAMBER • Split in the mesenchyme posterior to the developing iris and anterior to the developing lens. • Anterior and Posterior Chamber communicates when the pupillary membrane disappears and pupil is formed • Aqueous humor fills these two chambers
  52. 52. VASCULATURE • At 5-6mm stage simple endothelial tubes bud from internal carotid artery grow towards developing optic cup • 2 Main vessels in this period  dorsal ophthalmic artery  ventral ophthalmic artery Invests the more medial portion of the cup & almost disappears except a portion of Long Posterior nasal ciliary artery(LPNCA) At 3rd week branches to form hyaloid artery which enters the embryonic fissure at 7-8mm stage Becomes definative dorsal opthalmic artery at th week Supplies the TLPCA, SPCA,CRA • The system drains into future cavernous sinuses by way of plexuses
  53. 53. HYALOID VASCULAR SYSTEM Embryonic intraocular vasculature system is divided into 2 component  Anterior system  In the region of iris  Composed of pupillary membrane  Posterior retrolental system  within vitreous  composed of    hyaloid artery vasa hyaloidea propria tunica vasculosa lentis
  54. 54. ANTERIOR SYSTEM  MAJOR ARTERIAL CIRCLE OF IRIS: anastomosis of the anterior ciliary arteries with the Long posterior ciliary arteries, near the root of the iris  PUPILLARY MEMBRANE: Radial vascular loops over the surface of the iris and lens+ formed by Annular vessel & major arterial circle.  MINOR ARTERIAL CIRCLE OF IRIS: Central portion of the pupillary arcades disappear but the peripheral remains as minor arcade.
  55. 55. Applied Anatomy • Persistent pupillary membrane
  56. 56. POSTERIOR SYSTEM  HYALOID ARTERY  Branches from the Dorsal ophthalmic artery- 3rd week- enters the optic cup via embryonic fissure  Grows anteriorly towards lens.  Supplies lens, vitreous and developing optic nerve.  By 4th month many branches bud off to form main branches of central retinal artery- the first permanent intraocular blood supply.  Continues to be an important source of nutrition till the beginning of 8th month of gestation.
  57. 57.  VASA HYALOIDA PROPRIA  Small capillary branches that extend from main trunk of hyaloid artery through out vitreous  Anastomose with each others and with tunica vasculosa lentis
  58. 58.  TUNICA VASCULOSA LENTIS  Formed by terminal branches of main trunk of hyaloid artery  2 branches  Anterior tunica vasculosa lentis  Posterior tunica vasculosa lentis  Extend around equator of lens to form lateral tunica vasculosa lentis/ capsulopupillary vessels  Anastomose with anterior tunica vasculosa lentis and makes a drainage system through annular vessels and later in gestation through ciliary vessels
  59. 59. Long Posterior ciliary arteries Anterior vascular capsule capsulopupillary portion Posterior vascular capsule Hyaloid Artery Tunica Vasculosa Lentis
  60. 60. HYALOID VASCULAR SYSTEM(cont..) • Begins regressing even before some of its components have not reached peak of development • Stimulus – unknown • 1st to regress  vasa hyaloida propria  tunica vasculosa lentis Finally main hyaloid artery
  61. 61. RETINAL CIRCULATION • By 7th -8th month of gestation, retinal vessels would have extended nasally to ora serrata but only to equator temporally • Vessels reach ora on temporal region only close to term and even after birth • APPLIED ANATOMY: Retinopathy of prematurityexcessive O2 in premature infantsvasoconstrictionobliterated veinsneovascularizationvascular area is nonstretchable (detaches)/ non-vascular area is stretchable.
  62. 62. UVEAL CIRCULATION  Develops from vasoformative paraxial mesoderm that surrounds the optic cup  6th wk-  Common temporal ciliary artery branch of dorsal ophthalmic artery runs along the temporal aspect of stalk & cup  Common Nasal ciliary artery branches of ventral ophthalmic artery runs along the nasal aspect of stalk & cup  These two vessels are the precursors of long posterior ciliary artery  These anastomose with each other posteriorly & anteriorly to form greater circle of iris
  63. 63. • 3rd month 12 -15 short posterior ciliary arteries develop from dorsal ophthalmic artery Anterior ciliary artery Develops from small tributaries from muscular & lacrimal branch of ophthalmic artery Anastomose with branches of long posterior ciliary artery
  64. 64.  Develop as folds of surface ectoderm above and below the developing cornea.  Folds fuse at 3rd month intrauterine life.  A closed space, conjunctival sac, exists in front of cornea.  Separation of eyelids starts by 5 month and completes by the 7th month. EYELIDS
  65. 65.  Connective tissue and tarsal plates Mesenchymal core of the lids  Eyelashes epithelial buds from surface ectoderm  First appear in upper lid Arranged in 2-3 rows  Glands of Zeis and Moll ciliary follicles  Tarsal/Meibomian glands develop as columns of ectodermal cells from lid margins Gland of Zeis and Moll Mebomian gland Orbicularis Oculi Cornea
  66. 66. APPLIED ANATOMY- EYELID • cryptophthalmos Failure of separation of eyelids – In cases of cryptophthalmos usually cornea is absent • Ankyloblepharon adhesion of eyelids • Epicanthal Foldspalpebralis, tarsalis, supraciliary and inversus
  67. 67. EXTRAOCULAR MUSCLES • From the mesenchyme in the region of developing eyeball – four recti muscles superior and inferior oblique muscles • Initially represented as a single mass of mesenchyme • Later separates into distinct muscles, first at insertions and later at their origins
  68. 68. • Levator palpabrae superioris formed last splitting from the mesenchyme that forms the superior rectus • During development, muscles become associated with IIIrd, IVth and VIth cranial nerves • Orbicularis oculi muscle• Mesenchyme of 2nd pharyngeal arch • Invades eyelids • Supplied by VIIth cranial nerve
  69. 69. APPLIED ANATOMY OF EOM  During congenital ptosis there is paralysis of superior rectus muscle .
  70. 70. LACRIMAL GLAND  Form as series of epithelial buds, which grow superolaterally from superior fornix of conjunctiva into the underlying mesenchyme  Buds canalize- secretary units multiple ducts  With the development of Levator palpabrae superioris, gland divides into orbital part  palpebral part  No tear production until third month after birth
  71. 71. LACRIMAL SAC AND NASOLACRIMAL DUCT • Develop as solid cord of ectodermal cells between the nasal process and maxillary process of the developing face • The cord later canalizes – nasolacrimal duct • Superior end dilates to form lacrimal sac • Further cellular proliferation forms lacrimal ducts which enters each eyelid
  72. 72. APPLIED ANATOMY  At junction of advancing cords there is a membranous plate, and it is at this site that block of NLD usually occurs in congenital NLD block  Incomplete canalization watering from eyeinfection of the lacrimal duct and sac
  73. 73. ORBIT  Orbital bones  mesenchyme that encircles the optic vesicle  Medial wall – lateral nasal process  Lateral and inferior wall- maxillary process  Superior wall- mesenchymal capsule of forebrain  Posteriorly – from bones of base of skull  Orbital bones form in membrane, except those forming the posterior part which form in cartilage
  74. 74. • Axis of orbitAt 1st month- 180 degrees laterally  At 2nd month - this angle begins to lessen  At 3rd month 72 degrees  Later stabilises at 45 degrees • Development of eyeball is at faster rate than of orbit; at 6th intrauterine life anterior half of eyeball projects beyond orbital opening
  75. 75. Primordial tissues and its derivatives • Neuroectoderm • Surface ectoderm • Mesoderm
  76. 76. SUMMARY OF OCULAR EMBRYOGENESIS rd week • Optic groove appears th week • Optic pit develops into opticvesicle • Lens plate forms • Embryonic Fissure develops st month • Lens pit then Lens vesicle form • Hyaloid vessels develop
  77. 77. ½ month • Closure of embryonic fissure • Proliferation of neural retinal cells • Appearance of eyelid folds and nasolacrimal duct th week • Formation of embryonic nucleus of the lens • Sclera begins to form • Migration of waves of neural crest • First wave: formation of corneal and trabecular endothelium • Second wave: formation of corneal stroma • Third wave: formation of Iris stroma
  78. 78. rd month • Differentiation of precursors of Rods and Cones • Anterior Chamber appears • Fetal nucleus starts to develop • Sclera condenses • Eyelid folds lengthen and fuse th month • Formation of Retinal vasculature begins • Hyaloid vessels begin to regress • Formation of physiological optic dsc and Lamina Cribosa • Canal of Schlemn appears • Bowman’s membrane develop • Formation of major arterial circle and spinchter muscle of Iris
  79. 79. th month • Photoreceptors differentiate • Eyelid separation begins th month • Differentiation of dilator pupillae muscle • Nasolacrimal system becomes patent • Cones differentiate th month • Rods differentiate • Myelination of optic nerve begins • Posterior movement of anterior chamber angle • Retinal vessles start reaching nasal periphery
  80. 80. th month • Completion of anterior chamber angle formation • hyaloid vessels disappear th month • Retinal vessels reach temporal periphery • Pupillary membrane disappears After birth • Macular region of the retina develops further
  81. 81. REFERENCES  Peyman, Gholam A., Sanders and Goldberg, Principles and practice of Opthalmology(Vol.1),1st Edition,Jaypee:Delhi7,1987  Snell, Richard s. and Michael A. lemp, Clinical anatomy of the eye,2nd Edition, India:Blackwell science,1998.  Ramanjit Sihota, Radhika Tandon, Parson’s diseases of Eye- st Edition, Elsevier 2011  T.W. Sadler, Langman’s Medical Embryology, 9th Edition  Internet Resources