Australian scientists have identified, for the first time, specific genetic changes that sharply increase the risk of the most sight-threatening forms of age-related macular degeneration (AMD), offering a crucial lead for developing new therapies that could intervene before irreversible vision loss occurs.
The discovery, published in Nature Communications, zeroes in on the genetic drivers of reticular pseudodrusen, retinal deposits present in up to 60 per cent of people with advanced AMD and strongly associated with accelerated vision decline. The study was led by researchers from the Centre for Eye Research Australia, WEHI, and the University of Melbourne, working with international collaborators.
AMD is a major global cause of permanent blindness in people over 50, affecting more than 196 million individuals worldwide. The condition results from the death of light-sensitive cells in the macula, progressively eroding central vision. Despite its prevalence, clinicians still struggle to predict which patients will rapidly deteriorate, and existing treatments only slow progression once substantial retinal damage has already occurred.
In this extensive genome-wide analysis, the first of its kind focused specifically on reticular pseudodrusen, the team identified a strong association between these deposits and genetic variations on Chromosome 10. In contrast, they found no link to well-known AMD-related genes on Chromosome 1, including complement factor H (CFH), which has long been the focus of therapeutic development.
Eye imaging of individuals carrying Chromosome 10 variants also revealed a thinner retina, suggesting structural changes that may underpin more severe disease. Researchers say this will be a key focus for future investigation.
Study co-lead Professor Robyn Guymer AM from the Centre for Eye Research Australia said the findings challenge long-held assumptions that AMD is a single disease with uniform mechanisms.
“Reticular pseudodrusen deposits, visible in eye scans, have been linked to worse visual function and poorer treatment outcomes,” she said. “Our research has now identified which of the genetic changes appear to be driving this more serious form of AMD. This discovery provides a crucial lead for developing new drugs that target these changes—potentially preventing vision loss before it begins.”
Co-lead Professor Melanie Bahlo AM from WEHI said the study represents a significant shift in AMD genetics research.
“In 2005, researchers first linked changes on Chromosome 1—including the complement factor H gene—to AMD,” she said. “Recently, new treatments targeting these changes have shown modest success in slowing down the disease. Our study is the first to suggest that reticular pseudodrusen deposits are driven by pathways associated with Chromosome 10 but not by the well-known AMD-related genes on Chromosome 1.
“This is a significant finding. It demonstrates the need to explore how genetic changes on Chromosome 10 affect retinal structure and to develop therapies that go beyond complement-factor targeting to prevent sight-threatening deposits on the retina.”
A National Health and Medical Research Council Synergy Grant supported the study.