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

Dr Sarah Doyle, Trinity College Dublin

Commencing in 2018, this 3-year project is co-funded by Fighting Blindness and the Health Research Board (HRB) under the MRCG-HRB co-funding scheme. Through this study, Dr Doyle and her team at TCD will delve deeper into the mechanisms of retinal degeneration. We spoke with Dr Doyle to learn a little more.

Can you tell us a little more about your research project?

Retinal degenerations including age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are among the leading causes of sight loss in the world. In fact, the number of individuals affected by AMD is expected to reach 288 million globally by 2040.

A number of factors lead to retinal degeneration, but ultimately the end-point is loss of light sensitive cells in the retina called photoreceptors. Scientists are now trying to better understand pro-death or pro-survival traits in the retina. In our previous work on neurodegenerative diseases, we studied a molecule called SARM1 (selective androgen receptor modulator one). This molecule is highly efficient at triggering cell death in the brain following a response to a variety of insults. As such, SARM1 is termed an ‘executioner protein’. The retina is considered an extension of the brain and central nervous system but as of yet, no work investigating the role of SARM1 in the retina has been reported. We want to explore this molecule further in the context of retinal degeneration.

Should SARM1 be identified as a player in retinal degeneration, this research study could provide new targets for therapeutic development. This is particularly exciting, as blockers of SARM1 are currently in development for degenerative diseases of the brain.

What attracted you to retinal research?

It was through a social conversation with a retinal researcher that I now find myself in this field. As a biochemist with an interest in understanding how our immune system recognises danger signals, this serendipitous conversation about AMD piqued my curiosity and raised loads of questions about how our immune system responds to the early stages of disease. That was 8 years ago and I still find myself with more questions than answers when it comes to the role the immune system plays in retinal degenerations.

Within the next five years, where do you expect great advances to be made in vision research?

I think we will see gene therapy continue to excite not only the vision research world but the medical world in general in the 5 coming years.

What are your other interests?

I have a programme of research in paediatric immunology. This is also really fascinating and involves the study of some of the same pathways we are looking at in our retina studies.