of the hyaloid artery become sporadically occluded by macrophages prior to their gradual atrophy. Placental growth factor and vascular endothelial growth factor appear to be involved in hyaloid regression. Proximal arteriolar vasoconstriction at birth precedes regression of the major hyaloid vasculature. Atrophy of the pupillary membrane, TVL, and hyaloid artery occurs initially through apoptosis and later through cellular necrosis, and is usually complete by the time of eyelid opening 14 days postnatally.
Figure 1.4 The hyaloid vascular system and TVL.
The clinical lens anomaly known as Mittendorf's dot is a small (1 mm) area of fibrosis on the posterior lens capsule, and it is a manifestation of incomplete regression of the hyaloid artery where it was attached to the posterior lens capsule. Bergmeister's papilla represents a remnant of the hyaloid vasculature consisting of a small, fibrous glial tuft of tissue emanating from the center of the optic nerve. Both are frequently observed as incidental clinical findings.
Development of the Cornea and Anterior Chamber
The anterior margins of the optic cup advance beneath the surface ectoderm and adjacent neural crest mesenchyme after lens vesicle detachment (day 25 in the dog). The surface ectoderm overlying the optic cup (i.e., the presumptive corneal epithelium) secretes a thick matrix, the 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. This loosely arranged mesenchyme fills the future anterior chamber and gives rise to the corneal endothelium and stroma, anterior iris stroma, ciliary muscle, and most structures of the iridocorneal angle (ICA). The presence of an adjacent lens vesicle is required for induction of corneal endothelium, identified by their production of the cell adhesion molecule, N‐cadherin. Patches of endothelium become confluent and develop zonulae occludentes during days 30–35 in the dog, and during this period, Descemet's membrane also forms.
Neural crest migration anterior to the lens forms the corneal stroma and iris stroma also results in formation of a solid sheet of mesenchymal tissue, which ultimately remodels to form the anterior chamber. The portion of this sheet that bridges the future pupil is called the pupillary membrane. Vessels within the pupillary membrane form the TVL, which surrounds and nourishes the lens. These vessels are continuous with those of the primary vitreous (i.e., hyaloid). The vascular endothelium is the only intraocular tissue of mesodermal origin; even the vascular smooth muscle cells and pericytes, which originate from mesoderm in the rest of the body, are of neural crest origin. In the dog, atrophy of the pupillary membrane begins by day 45 of gestation and continues during the first two postnatal weeks. Separation of the corneal mesenchyme (neural crest cell origin) from the lens (surface ectoderm origin) results in formation of the anterior chamber.
Development of the Iris, Ciliary Body, and Iridocorneal Angle
The two layers of the optic cup (neuroectoderm origin) consist of an inner, nonpigmented layer and an outer, pigmented layer. Both the pigmented and nonpigmented epithelia of the iris and the ciliary body develop from the anterior aspect of the optic cup; the retina develops from the posterior optic cup. The optic vesicle is organized with all cell apices directed to the center of the vesicle. During optic cup invagination, the apices of the inner and outer epithelial layers become adjacent. Thus, the cells of the optic cup are oriented apex to apex.
A thin, periodic acid–Schiff (PAS)‐positive basal lamina lines the inner aspect (i.e., vitreous side) of the nonpigmented epithelium and retina (i.e., inner limiting membrane). By approximately day 40 of gestation in the dog, both the pigmented and nonpigmented epithelial cells show apical cilia that project into the intercellular space. These changes probably represent the first production of aqueous humor.
The iris stroma develops from the anterior segment mesenchymal tissue (neural crest cell origin), and the iris pigmented and nonpigmented epithelia originate from the neural ectoderm of the optic cup. The smooth muscle of the pupillary sphincter and dilator muscles ultimately differentiate from these epithelial layers, and they represent the only mammalian muscles of neural ectodermal origin. In avian species, however, the skeletal muscle cells in the iris are of neural crest origin, with a possible small contribution of mesoderm to the ventral portion.
Differential growth of the optic cup epithelial layers results in folding of the inner layer, representing early, anterior ciliary processes. The ciliary body epithelium develops from the neuroectoderm of the anterior optic cup, and the underlying mesenchyme differentiates into the ciliary muscles. Extracellular matrix secreted by the ciliary epithelium becomes the tertiary vitreous and, ultimately, develops into lens zonules.
The three phases of iridocorneal angle (ICA) maturation include (i) the separation of anterior mesenchyme into corneoscleral and iridociliary regions (i.e., trabecular primordium formation), followed by differentiation of ciliary muscle and folding of the neural ectoderm into ciliary processes; (ii) the enlargement of the corneal trabeculae and development of clefts in the area of the trabecular meshwork; and (iii) the postnatal remodeling of the drainage angle, associated with cellular necrosis and phagocytosis by macrophages, resulting in opening of clefts in the trabecular meshwork and outflow pathways.
In species born with congenitally fused eyelids (i.e., dog and cat), development of the anterior chamber continues during this postnatal period before eyelid opening. At birth, the peripheral iris and cornea are in contact with maturation of pectinate ligaments by three weeks and rarefaction of the uveal and corneoscleral trabecular meshworks to their adult state during the first eight weeks after birth.
Retina and Optic Nerve Development
Infolding of the neuroectodermal optic vesicle results in a bilayered optic cup with the apices of these two cell layers in direct contact. Primitive optic vesicle cells are columnar, but by 20 days of gestation in the dog, they form a cuboidal layer containing the first melanin granules in the developing embryo. The neurosensory retina develops from the inner nonpigmented layer of the optic cup and the retinal pigment epithelium (RPE) originates from the outer, pigmented layer. Bruch's membrane (the basal lamina of the RPE) is first seen during this time, and becomes well developed over the next week, when the choriocapillaris is developing. By day 45, the RPE cells take on a hexagonal cross‐sectional shape and develop microvilli that interdigitate with projections from photoreceptors of the nonpigmented (inner) layer of the optic cup.
At the time of lens placode induction, the retinal primordium consists of an outer, nuclear zone and an inner, marginal (anuclear) zone. This process forms the inner and outer neuroblastic layers, separated by their cell processes that make up the transient fiber layer of Chievitz. Cellular differentiation progresses from inner to outer layers and, regionally, from central to peripheral locations. Peripheral retinal differentiation may lag behind that occurring in the central retina by three to eight days in the dog. Retinal ganglion cells develop first within the inner neuroblastic layer, and axons of the ganglion cells collectively form the optic nerve. Cell bodies of the Müller and amacrine cells differentiate in the inner portion of the outer neuroblastic layer. Horizontal cells are found in the middle of this layer; the bipolar cells and photoreceptors mature last, in the outermost zone of the retina.
Significant retinal differentiation continues postnatally, particularly in species born with fused eyelids. At birth, the canine retina has reached a stage of development equivalent to the human at three to four months of gestation. In the kitten, all ganglion cells and central retinal cells are present at birth with continued proliferation in the peripheral retina continuing during the first two to three postnatal weeks in dogs and cats.
Sclera,
