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The pathogenesis of dry eye involves several key factors, including tear film instability, hyperosmolarity, chronic ocular surface inflammation, and neurosensory abnormalities. The ocular surface expresses a diverse array of ion channels, which play essential physiological roles in maintaining tear film stability, regulating osmotic pressure, balancing ion transport, and modulating inflammatory responses. This review systematically elucidates the relationship between ion channels and dry eye disease through three key aspects: the distribution and physiological functions of ion channels in ocular surface tissues, the therapeutic efficacy and mechanistic basis of ion channel targeted modulators in dry eye treatment, and a comprehensive classification of molecular mechanisms underlying ion channel targeted therapies for dry eye. Research on these targeted mechanisms establishes a theoretical foundation for clinical dry eye management and provides innovative strategies for developing novel ion channel based therapeutics.<\/jats:p>","DOI":"10.1096\/fj.202601064r","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:06:00Z","timestamp":1783451160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ion Channels and Dry Eye Disease: From Physiological Functions to Targeted Therapeutic Mechanisms"],"prefix":"10.1096","volume":"40","author":[{"given":"Jian","family":"Shen","sequence":"first","affiliation":[{"name":"School of Chemical Engineering and Technology Hebei University of Technology  Tianjin China"},{"name":"Key Laboratory of Molecular Biophysics of Hebei Province, Institute of Biophysics, School of Health Sciences and Biomedical Engineering Hebei University of Technology  Tianjin 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