The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness.
Aberrant ocular morphogenesis during embryonic development frequently results in reduced visual acuity or blindness. Morphological development of the eye begins with evagination of retinal precursors from the forebrain to produce bilateral optic vesicles and subsequent invagination of the associated ectoderm to create the lens.
Each optic vesicle reorganizes into a bilayered optic cup, with the distal (lens-facing) layer forming the presumptive neural retina and the proximal layer forming the retinal pigmented epithelium (RPE). The posterior segment of the developing eye receives two vascular supplies.
The transient hyaloid vasculature is a plexus between the retina and lens, and is connected to the hyaloid artery, which enters the eye via the inferior fissure. A second circulatory system, the choroidal vasculature, grows over the surface of the optic cup to nourish the RPE and the light-sensing photoreceptor cells in the outer retina.
In this manuscript, they classify superior coloboma as a separate disease with a developmental origin distinct from, but comparable to, inferior coloboma. Eight patients display gaps in tissues of the superior eye, including retina, lens, and iris. They demonstrated the existence of a transient dorsal groove in vertebrate eye development that is conserved amongst fish, chick, newt and mouse.
Failure to close the superior ocular sulcus can result in adult zebrafish displaying a phenotype that resembles superior coloboma. Furthermore, it supports the evolutionary conservation of the SOS amongst vertebrates, an evolutionary distance of some 450 million years. Eye morphogenesis and patterning are dependent on multiple signaling pathways, in addition to Bmp and RA.
The rare incidence of superior coloboma argues that the disorder is unlikely caused by simple, single-gene inheritance. Rather, a model incorporating multi-gene inheritance or incomplete penetrance is more plausible. Seven of the eight patients with superior coloboma in the current study display unilateral disease, also a common characteristic of inferior coloboma.
Further studies will be needed to discern the exact mechanisms of sulcus formation and resolution, and to more deeply analyze the causes of superior coloboma.