Roles of ocular vasculature in retinal neurogenesis

Background: the vertebrate neural retina is a complex structure comprising five major classes of neurons and glial cells, arranged in a stereotyped laminar pattern. This structure, is already present in zebrafish embryos at three days post-fertilization. The retina develops from a proliferative neuroepithelium under the regulatory influence of factors intrinsic to the retinal progenitors in the neuroepithelium and extrinsic factors from surrounding tissues such as blood vessels, that influence its morphogenesis and differentiation. Whether and how ocular vessels influence retinal development is largely unknown.

The poor knowledge of possible roles in the regulatory of morphogenesis and differentiation by the ocular vessels, is because vasculature is required for delivery of oxygen and nutrients from very early stages of development in mammalian models. We are using the embryonic zebrafish model, in which oxygenation needs of developing tissues at early stages can be supplied by diffusion and not by vasculature-mediated delivery.

Results: We find that the absence of ocular vessels results in severe retinal malformations, supporting a function for the vasculature in regulating retinal development. In contrast, zebrafish embryos that have blood vessels, but no actively circulating blood, have milder abnormalities, while, embryos with vasculature and circulation but no red blood cells, have normal-looking retinas. Additional analyses identify an extended period of proliferation in retinas without vessels or circulation and molecular analyses begin to identify mechanisms that regulate the abnormal development of these retinas.

Conclusions: Our findings suggest that factors derived from the endothelial cells and the circulatory system are important for development of the neural retina.