Restoring the mucin barrier: Advances in secretagogue therapies for ocular surface disorders

Mucins are essential components of the ocular surface, ensuring epithelial protection, tear film stability, and immune regulation. Mucin deficiency contributes to a spectrum of ocular surface disorders, including dry eye disease, allergic conjunctivitis, and cicatricial conditions such as Stevens-Johnson syndrome and ocular graft-versus-host disease. This review outlines current knowledge of mucin biology, regulatory mechanisms, and emerging therapeutic applications of mucin secretagogues in ocular surface disorders. Signaling cascades involving EGFR activation, MAPK phosphorylation, cholinergic and adrenergic stimulation, and cytokine-mediated modulation (e.g., interleukin-13, tumor necrosis factor-α) govern mucin transcription and goblet cell function. Clinically approved secretagogues such as diquafosol and rebamipide improve mucin expression and epithelial healing, while biologics, gene therapies, and nutraceutical compounds are actively being explored. Advancing these therapies may enable more targeted and durable restoration of ocular surface integrity across a range of mucin-deficient diseases. We searched for related research on PubMed using the terms "Mucin" and "Mucin secretagogues," along with keywords such as "dry eye," "goblet cell," and "ocular surface disorder." Articles related to mucin secretagogues published within the last 10 years were reviewed.