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.
年龄相关性黄斑变性(AMD)是老年人不可逆视力丧失的主要原因之一,受遗传和环境风险因素的综合影响。虽然AMD中的遗传关联已得到充分证实,但疾病发生和进展的分子机制仍知之甚少。越来越多的证据表明,表观遗传修饰可能是调节基因-环境相互作用的潜在缺失环节。本综述纳入了关于DNA甲基化的最新发现,包括影响诸如沉默交配型信息调节2同源物1(SIRT1)、谷胱甘肽S-转移酶同工型(GST)和SKI原癌基因等基因的高甲基化和低甲基化模式,这些模式可能影响AMD的关键病理生理驱动因素。我们还研究了组蛋白修饰模式、染色质可及性、长链非编码RNA(lncRNA)在AMD发病机制以及调节与该疾病病理生理学相关途径中的状态。虽然眼部表观遗传学领域仍处于起步阶段,但迄今为止积累的证据表明表观遗传调控在AMD中发挥着越来越重要的作用,临床前研究已为表观遗传学作为未来治疗途径的前景产生了有希望的发现。