Project: Elucidation of the role of SARM1 in retinal homeostasis and oxidative stress-induced retinal degeneration.
Start date: 2018
Award amount: €341,781.00 – Fighting Blindness contribution is €150,000.
Dr. Sarah Doyle Ph.D is Associate Professor in Immunology, Department of Clinical Medicine at the School of Medicine, Trinity College of Dublin and Head of the Immunobiology Research Group.
In 2023 Dr Doyle was appointed Director for Research at the School of Medicine, Trinity College. Also in 2023 Dr Doyle received a prestigious ERC Consolidator Grant.
Dr Doyle is also a co-Principal Investigator on the EYE-D project which Fighting Blindness co-funds.
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 (Retinal pigment epithelium (RPE), 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 aimed 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, prior to this project a role for SARM1 in triggering death of photoreceptor cells or their supporting RPE cells had not been investigated.
Our research has established that SARM1 is a key executioner of photoreceptors during the process of retinal degeneration. More specifically, using mouse models of disease our research has shown that:
One of the key ‘take home messages’ from our work is that even if we only block half the amount of SARM1 in the retina we still see significant protection of photoreceptor cells and vision.
This is very exciting as it makes SARM1 a very attractive target for therapeutic treatment to slow blindness. Even more exciting is that development of SARM1-blockers for degenerative diseases of the brain are already underway. These can now be considered for retinal disease as well.
Find out more Dr Sarah Doyle’s research in the video below:
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.
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.
This project is now reaching its end and below is the list of publications that have come from it:
2022:
2021:
2020: