Researchers Discover Novel Approach to Combat AMD

Increasing the levels of a key protein in retinal cells could help protect against age-related macular degeneration (AMD), finds a new discovery made by researchers from the UK, US, Germany (Department of Genetic Epidemiology, University of Regensburg) and Australia.

RPE cells following IRAK-M gene therapy. Image: Liu et al./Science Translational Medicine
RPE cells following IRAK-M gene therapy. Image: Liu et al./Science Translational Medicine

Progression of age-related macular degeneration (AMD) affects around 200-million people worldwide. This number is expected to rise to 288-million by 2040 as the population ages.  This new breakthrough could lead to new and more effective AMD treatments.

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). 

In this study, researchers 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 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.

The University of Bristol-led findings have been published today in Science Translational Medicine and are featured on the front cover.

Andrew Dick, Professor of Ophthalmology from Bristol Medical School at the University of Bristol, Director of the UCL Institute of Ophthalmology and one of the study’s lead authors, says: “Our findings suggest that boosting a protein called IRAK-M could be a potential treatment strategy for AMD and could offer an exciting new therapeutic target for this common condition for which effective therapies remain elusive.”

Dr Jian Liu, the lead author and senior research scientist at the Academic Unit of Ophthalmology at the University of Bristol, adds: “Since age stands as the primary risk factor for AMD, the gradual decrease of IRAK-M levels with age and a further decline in AMD signifies intricate biological mechanisms underlying the disease’s development and suggests a potential marker of early AMD progression.”

The authors aim to help develop the therapies further through a new University of Bristol spin-out company called Cirrus Therapeutics.

Dr Ying Kai Chan, Cirrus Therapeutics co-founder and Chief Executive Officer, and one of the study’s co-lead authors, says: “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.”

The research was funded by the Rosetrees Trust; Stoneygate Trust; Underwood Trust; Macular Society; Sight Research UK; Moran Eye Center and Sharon Eccles Steele Center for Translational Medicine (SCTM) at the University of Utah, USA, and supported by the National Institute for Health and Care Research (NIHR) BRC Moorfields and UCL-Institute of Ophthalmology.

Source: University of Bristol

Paper: ‘Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration’ by Jian Liu et al. in Science Translational Medicine