MINI REVIEW article
Front. Genet.
Sec. RNA
This article is part of the Research TopicEpigenetic Modifications in Drugs and DiseasesView all 5 articles
Emerging Role of Epigenetic Mechanisms in Glaucoma and Their Translational Potential
Provisionally accepted
- King Saud University, Riyadh, Saudi Arabia
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Glaucoma, a leading cause of irreversible blindness, is a complex polygenic disease where significant clinical and genetic heterogeneity do not explain all glaucoma cases, highlighting the need for a deeper understanding of molecular mechanisms like epigenetics. This review examines the emerging role of key epigenetic mechanisms, specifically DNA methylation, histone modifications, and non-coding RNAs in glaucoma pathogenesis and their potential as biomarkers and therapeutic targets. We discuss how aberrant DNA methylation (e.g., GDF7 hypomethylation/CDKN2B hypermethylation) promotes trabecular meshwork fibrosis and increases optic nerve vulnerability, contributing to disease development and/or progression. The METTL23 histone methylation linked to retinal ganglion cell death at normal eye pressure, and disease-specific microRNA profiles further support the role of epigenetic involvement in glaucoma. The proof-of-concept studies of GDF7 neutralization in primate models and the OSK-factor reprogramming in aged and glaucoma mice models, show that epigenetic changes are reversible and can restore visual functions. DNA methylation-based epigenetic clocks identify glaucoma as an accelerated molecular aging process. Although promising, the current evidences are largely preclinical and long-term human data are still lacking. Nonetheless, the inherent reversible nature of epigenetics offers significant translational potential. Methylation, epigenetic clocks, and circulating microRNA profiles could enable early, non-invasive biomarkers for diagnosis and prognosis. Future efforts are needed to validate biomarkers in large cohorts and develop targeted epigenetic therapies. In conclusion, epigenetics is redefining our current understanding of glaucoma from a pressure-based disease to a modifiable link between genes and environment paving the way for personalized care for vision preservation beyond pressure-lowering treatments.
Keywords: biomarkers, DNA Methylation, epigenetics, Glaucoma, histonemodifications, neurodegeneration, non-coding RNA
Received: 05 Jan 2026; Accepted: 09 Feb 2026.
Copyright: © 2026 Kondkar, Sultan, Azad and Al-Obeidan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Altaf A Kondkar
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