Elucidation of the role of SARM1 in retinal homeostasis and oxidative stress induced retinal degeneration

Photoreceptor cells found in the back of our eyes convert light into signals that allow us to see. Death of these cells and the cells that nourish them, called RPE cells, is termed retinal degeneration and is characteristic of blinding diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa. Millions of people worldwide suffer varying degrees of vision-loss due to these irreversible eye conditions, in fact, the number of individuals suffering from AMD is expected to reach ~288 million globally by 2040. The process of cell-death is a programmed event that directs proteins in our cells to take on ?executioner? roles. Over the past decade great leaps have been made in identifying these executioner proteins and in understanding the pathways that lead to their activation. There are a wide range of causes behind cell-death in the eye, but ultimately the end-point for each is photoreceptor cell death. Identifying unifying pro-death or pro-survival traits in these diseases has the potential to offer global therapeutic approaches for facilitating the protection of visual function across multiple diseases. In this research proposal, we aim to investigate the role of the executioner molecule, called SARM1, in retinal degeneration. SARM1 has already been shown to be highly efficient at triggering cell death in brain cells in response to a variety of insults. The retina is an extension of the brain, however, a role for SARM1 in triggering death of photoreceptor cells or their supporting RPE cells has not been investigated. If, as our pilot data indicates, we discover that SARM1 is a key executioner in the process of retinal degeneration, our research will have provided a new therapeutic target to slow the progression of blinding diseases. This is particularly exciting, as development of SARM1-blockers for degenerative diseases of the brain are already underway.

Award Date
28 June 2018
Award Value
Principal Investigator
Dr Sarah Doyle
Host Institution
Trinity College Dublin
MRCG-HRB Joint Funding Scheme