DNA mmethylation in ocular surface diseases: bridging research and clinical applications

Abstract

The rising prevalence of ocular surface diseases, particularly dry eye disease and allergic conjunctivitis, contrasts with the continued limited understanding of the pathogenesis. Evidence indicates that aberrant methylation of immune-related genes—such as those within the interferon pathway—in lacrimal glands and peripheral immune cells promotes autoimmune responses in Sjögren’s syndrome-related dry eye disease (SS-DED). For allergic conjunctivitis, altered methylation in nasal mucosa and peripheral blood cells suggests the involvement of similar epigenetic mechanisms, although direct evidence remains limited. Additionally, environmental factors such as circadian rhythm disruption can influence ocular surface immune homeostasis and inflammatory responses through the modulation of DNA methylation patterns. Current understanding is constrained by reliance on animal models and surrogate tissues, with human ocular surface methylation profiles remaining largely unexplored. Future research must integrate single-cell multiomics to map cell-specific methylation dynamics, validate cross-tissue biomarkers, and functionally characterize key differentially methylated genes. Elucidating these epigenetic networks will enable the development of precise, methylation-based diagnostics and targeted therapies for the personalized management of ocular surface diseases.