Advances in molecular genetics and multi-omics of exfoliation syndrome

Exfoliation syndrome (XFS) is a systemic disorder of the extracellular matrix characterized by the progressive deposition of abnormal fibrillar material in the tissues of the anterior segment, and is a major cause of secondary glaucoma and irreversible vision loss worldwide. Despite the identification of multiple risk factors, the molecular pathogenesis of XFS remains incompletely understood. In addition to the well-recognized susceptibility variants in LOXL1 and CACNA1A, recent studies have identified strong associations between XFS risk and novel genetic loci, including CLU and CYP39A1. Beyond genetic influences, alterations in DNA methylation, non-coding RNA expression, protein profiles, and metabolic signatures have also been implicated in the development and progression of this disease. This review summarizes the molecular genetic mechanisms and multi-omics findings related to XFS, with the objective of establishing a theoretical foundation for the discovery of early diagnostic biomarkers and potential therapeutic targets.