Retinal Ganglion Cell Mechanisms of Differentiation and Survival

University Of California Santa Cruz, Santa Cruz CA

Investigators

Abstract

? DESCRIPTION (provided by applicant): The goal of this proposal is to understand the molecular mechanisms involved in the generation of non-image-forming retinal ganglion cell (RGC) circuits and their survival in the mammalian retina. Non-image-forming RGCs are necessary for mediating behaviors dependent on light, such as sleep/wake cycles and pupil constriction, and it includes the melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs). The interesting functional and survival properties of these RGCs are based on their unique molecular code. However, nothing is known about the molecular mechanisms that specify the identity or survival ability of the non-image-forming RGCs. The proposed research aims to elucidate these mechanisms through a combination of immunocytochemistry, transgenic mice, electrophysiology, and anatomical tracing techniques. Our lab has found a transcription factor, Tbr2, that is only expressed in the non-image-forming RGC class and is necessary for their formation. Additionally, other labs have recently found that ipRGCs, which express this transcription factor, preferentially survive after an optic nerve crush. Aim 1 will test the hypothesis that Tbr2 is sufficient to induce non-image-forming RGC types such as ipRGCs when ectopically expressed in progenitors. Aim 2 will test the contribution of Tbr2 to neuroprotection of RGCs. Overall, the results from these aims will aid in understanding how specificity is attained in the formation of retinal circuitry, and what are molecular mechanisms fo neuroprotection of RGCs. This knowledge is critical for the goal of finding successful therapies for treatment of retinal diseases and restoration of damaged circuits.