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Researchers find potential new target for eye disease therapy

Research led by scientists at Trinity College Dublin has pinpointed a potential new therapeutic target for treating retinal degeneration.

The work discovered that a protein (SARM1) involved in neuronal cell injury could also play a role in the progression of retinal degeneration.

Millions of people worldwide suffer varying degrees of vision-loss due to irreversible retinal degenerative diseases, such as age-related macular degeneration (AMD), the leading cause of sight loss in the elderly.

“Lots of different factors can initiate retinal degeneration and lead to severe visual impairment and eventual blindness, but ultimately the end-point is photoreceptor cell death. Although it seems unlikely the process of cell-death is – in fact – a programmed or organised event that directs proteins in our cells to take on ‘executioner’ roles,” noted Ema Ozaki, research fellow in clinical medicine at Trinity.

In this research, the team led by Dr Sarah Doyle, assistant professor in immunology at Trinity, investigated the role of one such ‘executioner protein’ called SARM1.

Research has already shown that SARM1 is highly efficient at triggering the degeneration of neuronal cells, but this research is the first to describe a role for SARM1 in photoreceptor cell biology.

“Our research indicates that SARM1 is likely to be a key executioner in the process of retinal degeneration, because if we remove it from our experimental model system this has the effect of delaying the photoreceptor cells from dying,” said Dr Doyle.

“This is an important finding because the first steps involved in processing ‘light into sight’ take place in the photoreceptors. As a result, losing photoreceptors ultimately equates to losing vision. For this reason, interventions that prevent or delay photoreceptor cell death are critical to preserve sight for as long as possible in people with degenerative retinal diseases.”

The research team was also able to show that the protected and surviving photoreceptors maintained their function and continued to transmit electrical signals to the optic nerve, thereby providing a new therapeutic target to slow the progression of blinding diseases.

“This is particularly exciting for the future because others have recently shown that a gene therapy approach for inhibiting SARM1 is effective in protecting against neuronal degeneration. We know that gene therapy is well suited as a treatment for retinal disease, so such an approach for inhibiting SARM1 activity may offer an option for protecting vision across multiple retinal degenerative diseases,” Dr Doyle added.

The research, involving experts from Trinity’s Schools of Medicine, Biochemisty and Immunology, Genetics and Microbiology, and Engineering, is published in the journal Life Science Alliance.

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