Boosting protein in eye cells could prevent vision loss

An international research team has found that increasing the levels of a key protein in the cells at the back of the eye could help protect against age-related macular degeneration (AMD) — the leading cause of vision loss among older adults.

Patients suffering from AMD often start with blurred vision or seeing a black dot in their central vision, which can ultimately expand to the point where there is no useful central vision. The condition primarily affects people over the age of 50, and the risk of developing AMD significantly increases with age.

Scientists believe that chronic inflammation, which is typical with aging, is associated with the reduction of a key immune regulatory protein called IRAK-M. This protein is crucial for protecting the retinal pigment epithelium (RPE), a layer of cells essential for maintaining a healthy retina. When RPE cells are damaged, it can result in serious eye conditions and vision loss.

In the new study, researchers led by the University of Bristol investigated the role of IRAK-M in AMD by examining genetic variations and their link to AMD risk. By studying IRAK-M levels in patient samples and mouse models of retinal degeneration, the team observed changes in retinal function in mice lacking the IRAK3 gene, which expresses the IRAK-M protein. They found that IRAK-M decreases with age, especially in the retinal pigment epithelium (RPE), and this decline is more pronounced in those with AMD.

The team then sought to explore whether increasing IRAK-M could protect retinal cells from degeneration in mouse models and whether it is a potential therapeutic target for macular degeneration. They show that increasing IRAK-M levels through RPE-specific gene delivery helps protect against the effects of aging and oxidative stress and reduces retinal degeneration. Their results were published in the journal Science Translational Medicine.

“Our findings suggest that boosting a protein called IRAK-M … could offer an exciting new therapeutic target for this common condition for which effective therapies remain elusive,” said Bristol’s Professor Andrew Dick, a lead author on the study.

“Since age stands as the primary risk factor for AMD, the gradual decrease of IRAK-M levels with age … signifies intricate biological mechanisms underlying the disease’s development and suggests a potential marker of early AMD progression,” added lead author Dr Jian Liu, also from the University of Bristol.

The authors aim to help develop the therapies further through a new University of Bristol spin-out company called Cirrus Therapeutics. The company’s co-founder and CEO, Dr Ying Kai Chan, said, “This discovery will build and improve upon current treatments for AMD, which are targeting single pathophysiology pathways. Our novel approach not only addresses the multiple pathways involved in treating AMD but also offers the most compelling and evidence-based strategy available today.”

Image caption: The front cover of June’s Science Translational Medicine shows rescued retinal pigment epithelium (RPE) cells following IRAK-M gene therapy. Image credit: Liu et al/Science Translational Medicine.