Transient receptor potential ion channels in dry eye disease: mechanisms, pharmacological targeting, and clinical translation
Year: 2026
Type: article
Abstract: Dry eye disease (DED) is a multifactorial, symptomatic disease characterized by loss of homeostasis of the tear film and/or ocular surface, with tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities acting as etiological factors. Transient receptor potential (TRP) channels are nonselective cation channels that translate thermal, osmotic, mechanical, and chemical cues into Ca 2+ signaling, neuronal activity, secretory reflexes, and inflammatory responses across the ocular surface. Among the TRP family members implicated in DED, TRPM8 has the most advanced translational evidence: it contributes to ocular surface cooling/wetness sensing and basal tearing, and the TRPM8 agonist acoltremon was approved by the United States Food and Drug Administration in 2025 for the signs and symptoms of DED in adults. TRPV1 links hyperosmotic stress to epithelial inflammatory signaling and nociception, but also participates in reparative neuroimmune responses after corneal injury. TRPA1 is strongly implicated in chemical nociception, neurogenic inflammation, and pain sensitization, whereas TRPV4 is better supported as a regulator of epithelial volume homeostasis and membrane-associated mucins. These channels therefore differ substantially in cellular context, disease-stage dependence, and clinical maturity. This review integrates current mechanistic, preclinical, and clinical evidence for TRPM8, TRPV1, TRPA1, and TRPV4, discusses emerging evidence for TRPP2, and proposes a phenotype-oriented framework for pharmacological targeting. Particular emphasis is placed on evidence hierarchy, unresolved controversies, long-term sensory safety, and biomarkers needed to advance precision TRP-directed therapy in DED.
Source: Frontiers in Pharmacology
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225827268