Embryology of the Eye Structures

Tertiary Vitreous

• Forms as a thick accumulation of collagen fibers between the lens equator and the optic cup, known as Drualt's bundle
• Precursor to the vitreous base and lens zonules
• Early lens zonular fibers appear to be continuous with the inner membrane of the non-pigmented epithelial layer
• Elastin and emulin have been identified in developing zonules and Descemet's membrane
• Traction of zonules contributes to lens expansion, and localized absence of zonules can lead to a flattened area of the lens, inaccurately referred to as a lens coloboma

Optic Nerve

• Axons from developing ganglion cells traverse through vacuolated cells in the inner wall of the optic stalk
• Glial cells form a sheath around the hyaloid artery
• As the artery regresses, the space between it and the glial sheath expands
• Bergmeister's papilla is a remnant of glial cells around the hyaloid artery
• Glial cells migrate into the optic nerve and establish the primitive optic disc
• Glial cells surrounding the optic nerve and those forming part of the lamina cribrosa originate from the inner layer of the optic stalk, derived from neural ectoderm
• Subsequently, a mesenchymal portion of the lamina cribrosa develops from neural crest origin
• Myelinization of the optic nerve initiates at the chiasm, progresses toward the eye, and reaches the optic disc after birth

Ocular Embryology and Congenital Malformations

• Gastrulation and neurulation:
  • Fertilization → zygote → morula (cluster of 12-16 cells)
  • Morula becomes blastocyst, which contains a fluid-filled cavity
  • Cells of the blastocyst form embryo proper and extraembryonic tissues (amnion and chorion)
  • Embryo bilaminar disc: hypoblast and epiblast
• Gastrulation: process where blastocyst becomes gastrula, forming mesodermal germ layer
• Day 10 in dogs, day 7 in mice, and day 15-20 in humans
• Primitive streak forms as a longitudinal groove within epiblast (future ectoderm)
• Epiblast cells migrate towards primitive streak, invaginate to form mesoderm
• Results in the 3 classic germ cell layers: Ectoderm, mesoderm, and endoderm
• Gastrulation proceeds in cranial-to-caudal progression, with cranial surface ectoderm proliferating to form bilateral elevations called neural folds (forming the brain)

Formation of the Optic Vesicle and Optic Cup

• Optic vesicle development starts with the emergence of optic sulci, which are paired outgrowths of the forebrain neural ectoderm
• Optic sulci are paired evaginations of forebrain neural ectoderm, around day 13 of gestation in dogs
• Concurrent with the closure of the neural tube, the optic sulci transform into optic vesicles
• Optic vesicle enlarges and approaches the basal lamina underlying the surface ectoderm
• Optic vesicle and optic stalk invaginate through growth and infolding
• Surface ectoderm in contact with optic vesicle thickens to form lens placode, which then invaginates with underlying neural ectoderm

Lens Formation

• Surface ectoderm becomes competent to respond to lens inducers
• Anterior neural plate produces inductive signals to give this area of ectoderm a "lens-forming bias"
• Optic vesicle then adheres to lens placode, ensuring alignment of lens and retinal in the visual axis
• Lens placode invaginates, forming a hollow sphere = lens vesicle
• Size of lens vesicle is determined by contact area of optic vesicle with surface ectoderm and ability of surface ectoderm to respond to induction of growth signals
• Abnormal orientation of optic vesicle can cause induction of a smaller lens vesicle
• Lens vesicle detachment leads to anterior chamber formation
• Induction of small lens vesicle that does not separate normally from surface ectoderm can lead to anterior segment dysgenesis

Vascular Development

• Hyaloid artery is the termination of the primitive ophthalmic artery, which branches off the internal ophthalmic artery
• Remains within the optic cup following closure of the optic fissure
• Branches round the posterior lens capsule and anastomoses with vessels in the pupillary membrane
• Hyaloid vascular network forms around the lens, providing nutrition to the lens and anterior segment
• Venous drainage occurs near the equatorial lens area, with no discrete hyaloid vein present
• Ciliary body begins to produce aqueous humor, which nourishes the lens, and the hyaloid artery starts to regress
• Regression of the hyaloid vasculature allows for the development of retinal vessels, primarily mediated by vascular endothelial growth factor (VEGF)-A

Development of the Cornea and Anterior Chamber

• After detachment of the lens vesicle, the anterior margins of the optic cup extend beneath the surface ectoderm, initiating corneal development
• Surface ectoderm above the optic cup secretes a thick matrix (primary stroma)
• Mesenchymal neural crest cells migrate between the surface ectoderm and the optic cup, using the basal lamina of the lens vesicle as a substrate
• Induction of corneal endothelium requires the presence of an adjacent lens vesicle
• Dehydration leads to a 50% reduction in stromal thickness, aided by the corneal endothelium, which develops tight junctions and forms Descemet's membrane
• Transparency of the cornea is achieved by the end of gestation in dogs, with subsequent postnatal changes in corneal thickness observed after eyelid opening

Development of the Iris, Ciliary Body, and Iridocorneal Angle

• The two layers of the optic cup are neuroectoderm in origin
• The iris and ciliary body develop from the anterior aspect of the optic cup, while the retina develops from the posterior aspect
• Optic vesicle is organized with all cell apices directed towards the center, so during invagination, apices of inner and outer epithelial layers become adjacent
• Both pigmented and nonpigmented epithelial cells develop apical cilia and show increased Golgi complexes and vesicles around day 40 of gestation in dogs
• Nonpigmented and pigmented epithelium of the iris and ciliary body originates from the neural ectoderm of the optic cup
• Stroma comes from neural crest cell origin (mesenchymal tissue)
• Differential growth of optic cup epithelial layers causes folding of the inner layer, representing early anterior ciliary processes

Retina and Optic Nerve Development

• The infolding of the neuroectodermal optic vesicle leads to the formation of a bilayered optic cup
• The outer layer of the optic cup, which originates from the optic vesicle, becomes cuboidal and develops melanin granules, forming the retinal pigment epithelium (RPE)
• The inner layer of the optic cup gives rise to the neurosensory retina
• Bruch's membrane, the basal lamina of the RPE, appears during this time, coinciding with the development of the choriocapillaris
• RPE cells adopt a hexagonal shape by day 45 in dogs and develop microvilli that interdigitate with projections from photoreceptors
• At the time of lens placode induction, the retinal primordium consists of an outer nuclear zone and an inner marginal (anuclear) zone
• Retinal histiogenesis involves cell proliferation in the nuclear zone, migration into the marginal zone, and differentiation into inner and outer neuroblastic layers