Kisswani Dana, Carroll Christina, Valdes-Mora Fatima, Rutar Matt
Faculty of Science and Technology, University of Canberra, Canberra, ACT 2617, Australia.
The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
Int J Mol Sci. 2025 Aug 6;26(15):7601. doi: 10.3390/ijms26157601.
Age-related macular degeneration () is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene-environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (), glutathione S-transferase isoform (), and SKI proto-oncogene (), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs () in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue.