On May 3rd, 2023, the University at Buffalo published a ground-breaking study in Cell Genomics, detailing the first genome-wide significant analysis of the epigenetics of age-related macular degeneration (AMD), a condition that affects 200 million adults worldwide and is a leading cause of vision loss in older adults. The study was conducted using rigorously phenotyped post-mortem eye tissue, collected from a unique biorepository over the past decade, and involved extensive collaboration between industry and academia, as well as basic scientists and clinicians.
The study identified 23 significant, genome-wide loci that are differentially methylated in AMD, allowing for a better understanding of the genetic mechanisms and pathways that contribute to the development of this disease. The researchers also discovered 1,000 differentially expressed genes, some of which present potential drug targets, and identified two novel genes that play a major mechanistic role in the pathophysiology of the disease.
Using a systems biology approach, the researchers characterized expression, methylation, and chromatin accessibility in both normal and diseased human tissue and conducted a molecular analysis of human macular tissues from 85 well-characterized donor eyes, allowing them to better understand the causes of AMD.
This research is especially significant because there are no animal models that can fully recapitulate AMD, and the architecture of the human eye is unique. Therefore, access to tissues affected by the disease is critical to uncovering disease mechanisms and developing appropriate therapies. The findings of this study demonstrate what can be achieved when industry and academia collaborate and when basic scientists and clinicians partner synergistically to address challenging medical conditions.
Funding for the study was provided by Genentech/Roche, The Macular Degeneration Foundation Inc., The Carl Marshall Reeves & Mildred Almen Reeves Foundation Inc., the National Institutes of Health, and Research to Prevent Blindness, with some individuals on the paper funded by the National Center for Advancing Translational Sciences and UB’s Clinical and Translational Science Institute.
