The role of retinal ganglion cell subtype in survival and regeneration

University Of Miami School Of Medicine, Coral Gables FL

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Abstract

? DESCRIPTION (provided by applicant): Optic neuropathies damage retinal ganglion cell (RGC) axons of the optic nerve, resulting in permanent visual deficits. Substantial progress has been made in our ability to promote axon regeneration following axonal injury, but regeneration remains limited to a small number of RGCs. RGCs are a heterogeneous population, with more than 30 described subtypes. Through the use of transgenic mouse lines it has been determined that an RGC's subtype may predict its regenerative capacity. The molecular mechanisms that regulate subtype dependent differences in regenerative capacity have just started to be identified. The goal of this proposal is to determine: i) whether distinct subtypes of RGC display different responses to axonal injury, and ii) the transcriptional differences that correlate with regenerative capacity. In Aim 1, I will use transgenic mouse lines to investigate how altering light sensitivity affects RGC regeneration. In Aim 2, I will investigate how distinct subtypes of RGC respond to injury. This will be determined by immunohistochemical detection of proteins important for regeneration. Finally, in Aim 3 of this study I will identify potential positive and negative regulators of RGC axon regeneration. RGC subtypes with contrasting regenerative capacities will be selected for subsequent RNA-sequencing. Differentially expressed genes will be identified and validated by RT-qPCR. These genes will serve as novel therapeutic targets to enhance the regeneration of all RGCs, a critical step towards restoring lost vision.