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ectoderm origin.

      Lens vesicle detachment is the initial event leading to formation of the chambers of the ocular anterior segment. This process is accompanied by active migration of epithelial cells out of the keratolenticular stalk, cellular necrosis, apoptosis, and basement membrane breakdown. Induction of a small lens vesicle that fails to undergo normal separation from the surface ectoderm is one of the characteristics of the teratogen‐induced anterior segment dysgenesis described in animal models.

Schematic illustration of cross section through optic cup and optic fissure.

      At birth, the lens consists almost entirely of lens nucleus, with minimal lens cortex. Lens cortex continues to develop from the anterior cuboidal epithelial cells, which remain mitotic throughout life. Differentiation of epithelial cells into secondary lens fibers occurs at the lens equator (i.e., lens bow). Lens fiber elongation is accompanied by a corresponding increase in cell volume and a decrease in intercellular space within the lens.

      The zonule fibers are termed the tertiary vitreous, but their origin remains uncertain. The zonules may form from the developing ciliary epithelium or the endothelium of the posterior tunica vasculosa lentis (TVL).

      Once the ciliary body begins actively producing aqueous humor, which circulates and nourishes the lens, the hyaloid system is no longer needed. The hyaloid vasculature and TVL reach their maximal development by day 45 in the dog and then begin to regress.

      As the peripheral hyaloid vasculature regresses, the retinal vessels develop. Spindle‐shaped mesenchymal cells from the wall of the hyaloid artery at the optic disc form buds (angiogenesis) that invade the nerve fiber layer.

Schematic illustration of 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.

      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.

      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

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