‘Executioner protein’ discovery could lead to new eye disease therapeutics

20 Apr 2020

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Researchers at Trinity have discovered a potential new therapeutic target for eye disease after studying the role of an ‘executioner protein’ in retinal degeneration.

Research led by a team from Trinity College Dublin (TCD) has helped pinpoint a potential therapeutic target for a disease that affects thousands in Ireland.

While millions of people worldwide live with vision loss due to irreversible retinal degenerative diseases, it’s estimated that 5,000 people in Ireland inherit retinal degenerations, with a further 80,000 known to live with age-related macular degeneration (AMD).

This latest research, published to the journal Life Science Alliance, has revealed a protein called SARM1 that is involved in neuronal cell injury, but could also play a role in the progression of retinal degeneration.

Photoreceptor cells are specialised neurons found in the back of our eyes that convert light into electrical signals that allow us to see. It is the death of these cells, and the cells that nourish them, that is termed retinal degeneration and is characteristic of blinding diseases such as AMD and retinitis pigmentosa.

Researchers said this report is the first to describe a role for SARM1, referred to as the ‘executioner protein’, in photoreceptor cell biology.

Delaying the executioner protein

“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 Sarah Doyle of the research team.

“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 team was also able to show that the remaining photoreceptors maintained their function and continued to transmit electrical signals to the optic nerve.

“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,” Doyle added.

“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.”

Colm Gorey was a senior journalist with Silicon Republic

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