Emerging role of epigenetic mechanisms in glaucoma and their translational potential.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and animal models with no new human clinical trial data.
PubMed 41809128 · doi:10.3389/fgene.2026.1781271
What was done
This narrative review synthesized published evidence regarding the roles of DNA methylation, histone modifications, and non-coding RNAs in glaucoma pathogenesis. It evaluated preclinical studies investigating epigenetic alterations in trabecular meshwork fibrosis, retinal ganglion cell survival, epigenetic aging clocks, and translational interventions such as GDF7 neutralization and OSK reprogramming factors.
What was found
The abstract reports qualitative mechanistic and preclinical findings without numerical data or statistical metrics. Aberrant DNA methylation (such as GDF7 hypomethylation and CDKN2B hypermethylation) was associated with trabecular meshwork fibrosis and optic nerve vulnerability. METTL23 histone methylation was linked to retinal ganglion cell death at normal intraocular pressure. Preclinical studies demonstrated that GDF7 neutralization in primate models and OSK-factor reprogramming in mouse models reversed epigenetic changes and restored visual function, while DNA methylation clocks reflected accelerated molecular aging in glaucoma.
Why it matters
Epigenetic processes present a conceptual shift in glaucoma research toward modifiable molecular pathways beyond intraocular pressure management, pointing to potential non-invasive biomarkers and visual-restoration therapies.
Limits
The findings are derived predominantly from in vitro and animal models, with no long-term human clinical data provided. The abstract lacks quantitative outcome measures, systematic review methodology, and specific cohort sample sizes. Clinical utility remains unproven pending validation in large prospective human cohorts.
Cited by
- contradicts Partial epigenetic reprogramming clinical trials are being conducted in patients with glaucoma.