Dr. Sarah Doyle

Commencing in 2018, this project is co-funded by Fighting Blindness and the Health Research Board (HRB) under the HRCI-HRB co-funding scheme. Through this study, Dr Doyle and her team at TCD investigated deeper the mechanisms of retinal degeneration. The project is now near completion, information on the results of the research can be found below.

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.

Headshot of Dr Sarah Doyle
Dr Sarah Doyle

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.


We spoke to Dr. Sarah Doyle about her project. Find out more about the project and Dr. Doyle below.

  1. What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?
  2. Please describe the results from the project and your next steps
  3. What attracted you to retinal research?
  4. What are your other research interests?


1. What are the overall aims of the project you are working on, including how it could have an impact on those affected by sight loss?

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.


2. Please describe the results from the project

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:

  • In a healthy eye SARM1 is kept in an inactive state, however, in models of Retinitis Pigmentosa and AMD we see that SARM1 is activated in the photoreceptor cells and this activation causes an energy crisis followed by death of the photoreceptors.
  • If we block the activity of SARM1 we can slow the rate at which the photoreceptors die and
  • Importantly we have shown that the cells that we have protected from death maintain their function and are still able to transmit electrical signals.
  • Through this project we have now established that SARM1 is found at high levels in the photoreceptor cells of the retina, but is not found in the supporting RPE cells.

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:


3. 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.

Doctor Sarah Doyle - Retina 2018
Dr. Sarah Doyle – Retina 2018

4. What are your other research 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.




This project is now reaching its end and below is the list of publications that have come from it:



  • Gibbons L, Ozaki E, Greene C, Trappe A, Carty M, Coppinger JA, Bowie AG, Campbell M and Doyle SL (2022) SARM1 Promotes Photoreceptor Degeneration in an Oxidative Stress Model of Retinal Degeneration. Front. Neurosci. 16:852114. Click here to find the full information about this study
  • Ozaki E, Delaney C, Campbell M, Doyle SL. Minocycline suppresses disease-associated microglia (DAM) in a model of photoreceptor cell degeneration. Exp Eye Res. 2022 Jan 25;217:108953. Click here to find the full information about this study


  • Mulfaul K, Doyle SL. In vitro Measurement of Membrane Attack Complex in RPE Cells. Bio Protoc. 2021 Feb 20;11(4):e3916. Click here to find the full information about this study


  • Ozaki E, Gibbons L, Neto NG, Kenna P, Carty M, Humphries M, Humphries P, Campbell M, Monaghan M, Bowie A, Doyle SL. SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration. Life Sci Alliance. 2020 Apr 20;3(5):e201900618. Click here to find the full information about this study
  • Doyle SL. The Persistence of Privilege for a Healthy Retina. Immunity. 2020 Aug 18;53(2):240-242. Click here to find the full information about this study
  • Mulfaul K, Ozaki E, Fernando N, Brennan K, Chirco KR, Connolly E, Greene C, Maminishkis A, Salomon RG, Linetsky M, Natoli R, Mullins RF, Campbell M, Doyle SL. Toll-like Receptor 2 Facilitates Oxidative Damage- Induced Retinal Degeneration. Cell Rep. 2020 Feb 18;30(7):2209-2224.e5. Click here to find the full information about this study
  • Wooff Y, Fernando N, Wong JHC, Dietrich C, Aggio-Bruce R, Chu-Tan JA, Robertson AAB, Doyle SL, Man SM, Natoli R. Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage- induced retinal degeneration. Sci Rep. 2020 Feb 10;10(1):2263. Click here to find the full information about this study


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