Figure 1.1 Development of the optic sulci, which are the first sign of eye development. Optic sulci on the inside of the forebrain vesicles consisting of neural ectoderm (shaded cells). The optic sulci evaginate toward the 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.