surface ectoderm as the forebrain vesicles simultaneously rotate inward to fuse.
The optic vesicle enlarges and, covered by its own basal lamina, approaches the basal lamina underlying the surface ectoderm. The optic vesicle appears to play a significant role in the induction and size determination of the palpebral fissure and of the orbital and periocular structure. An external bulge indicating the presence of the enlarging optic vesicle can be seen at approximately day 17 in the dog.
The optic vesicle and optic stalk invaginate through differential growth and infolding. Local apical contraction and physiological cell death have been identified during invagination. The surface ectoderm in contact with the optic vesicle thickens to form the lens placode, which then invaginates with the underlying neural ectoderm. The invaginating neural ectoderm folds onto itself as the space within the optic vesicle collapses, thus creating a double layer of neural ectoderm, the optic cup.
This process of optic vesicle/lens placode invagination progresses from inferior to superior, so the sides of the optic cup and stalk meet inferiorly in an area called the optic (choroid/retinal) fissure. Mesenchymal tissue (of primarily neural crest origin) surrounds and fills the optic cup, and by day 25 in the dog, the hyaloid artery develops from mesenchyme in the optic fissure. This artery courses from the optic stalk (i.e., the region of the future optic nerve) to the developing lens. The two edges of the optic fissure meet and initially fuse anterior to the optic stalk, with fusion then progressing anteriorly and posteriorly. This process is mediated by glycosaminoglycan (GAG)‐induced adhesion between the two edges of the fissure. Apoptosis has been identified in the inferior optic cup prior to formation of the optic fissure and, transiently, associated with its closure. Failure of this fissure to close normally may result in inferiorly located defects (i.e., colobomas) in the iris, choroid, or optic nerve. Colobomas other than those in the “typical” six‐o'clock location may occur through a different mechanism and are discussed later. Closure of the optic cup through fusion of the optic fissure allows intraocular pressure (IOP) to be established.
Lens Formation
Before contact with the optic vesicle, the surface ectoderm first becomes competent to respond to lens inducers. Inductive signals from the anterior neural plate give this area of ectoderm a “lens‐forming bias.” Signals from the optic vesicle are required for complete lens differentiation, and inhibitory signals from the cranial neural crest may suppress any residual lens‐forming bias in head ectoderm adjacent to the lens. Adhesion between the optic vesicle and surface ectoderm exists, but there is no direct cell contact. The basement membranes of the optic vesicle and the surface ectoderm remain separate and intact throughout the contact period.
Thickening of the lens placode can be seen on day 17 in the dog. A tight, extracellular matrix‐mediated adhesion between the optic vesicle and the surface ectoderm has been described. This anchoring effect on the mitotically active ectoderm results in cell crowding and elongation and in formation of a thickened placode. This adhesion between the optic vesicle and lens placode also assures alignment of the lens and retina in the visual axis.
The lens placode invaginates, forming a hollow sphere, now referred to as a lens vesicle (Figures 1.2 and 1.3). The size of the lens vesicle is determined by the contact area of the optic vesicle with the surface ectoderm and by the ability of the latter tissue to respond to induction. Aplasia may result from failure of lens induction or through later involutions of the lens vesicle, either before or after separation from the surface ectoderm.
Figure 1.2 Formation of the lens vesicle and optic cup. Note that the optic fissure is present, because the optic cup is not yet fused inferiorly. (a) Formation of lens vesicle and optic cup with inferior choroidal or optic fissure. Mesenchyme (M) surrounds the invaginating lens vesicle. (b) Surface ectoderm forms the lens vesicle with a hollow interior. Note that the optic cup and optic stalk are of surface 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.
Following detachment from the surface ectoderm (day 25 in the dog), the lens vesicle is lined by a monolayer of cuboidal cells surrounded by a basal lamina, the future lens capsule. The primitive retina promotes primary lens fiber formation in the adjacent lens epithelial cells. Thus, while the retina develops independently of the lens, the lens appears to be dependent on the retinal primordium for its differentiation. The primitive lens filled with primary lens fibers is the embryonic lens nucleus. In the adult, the embryonic nucleus is the central sphere inside the “Y” sutures; there are no sutures within the embryonal nucleus.
Figure 1.3 Cross section through optic cup and optic fissure. The lens vesicle is separated from the surface ectoderm. Mesenchyme (M) surrounds the developing lens vesicle, and the hyaloid artery is seen within the 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).
Vascular Development
The hyaloid artery is the termination of the primitive ophthalmic artery, a branch of the internal ophthalmic artery, and it remains within the optic cup following closure of the optic fissure. The hyaloid artery branches around the posterior lens capsule and continues anteriorly to anastomose with the network of vessels in the pupillary membrane (Figure 1.4). The pupillary membrane consists of vessels and mesenchyme overlying the anterior lens capsule. This hyaloid vascular network that forms around the lens is called the anterior and posterior TVL. The hyaloid artery and associated TVL provide nutrition to the lens and anterior segment during its period of rapid differentiation. Venous drainage occurs via a network near the equatorial lens, in the area where the ciliary body will eventually develop. There is no discrete hyaloid vein.
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.
Branches
