Effectiveness of a heparin-like glycosaminoglycan from snail mucus in a murine model of dry eye

BACKGROUND: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and epithelial injury, leading to discomfort and visual disturbance. Current treatments remain limited in efficacy and safety. A heparin-like glycosaminoglycan purified from the snail mucus of Achatina fulica (AFG) exhibits potential regenerative and anti-inflammatory properties. This study aimed to evaluate the therapeutic effectiveness and mechanism of AFG in DED. METHODS: The effects of AFG on human corneal epithelial (HCE) cells were assessed by cell viability, proliferation, migration, and qRT-PCR analyses of proliferation- and mucin-related genes. In vivo, a benzalkonium chloride (BAC)-induced murine model of DED was used to evaluate corneal integrity, tear production, histological changes, inflammatory infiltration, and molecular expression following topical AFG treatment. Gene and protein expression levels were examined using qRT-PCR, western blotting, and immunofluorescence. RESULTS: AFG showed no cytotoxicity toward HCE cells and significantly enhanced their proliferation and migration by upregulating K14, KI67, P63, MUC1, and MUC4. In the DED mouse model, topical AFG treatment markedly improved corneal integrity, increased tear secretion, and restored epithelial structure. AFG upregulated the expression of epithelial differentiation and repair markers (K12, K14, PAX6) while downregulating inflammatory genes (IL-1β, TNF-α, IL-6, MMP-9, CD45) and reducing macrophage infiltration. These effects collectively promoted corneal epithelial regeneration and tear film stabilization. CONCLUSIONS: AFG alleviates dry eye disease by enhancing corneal epithelial proliferation, promoting mucin secretion, and suppressing inflammation. Its heparin-like glycosaminoglycan structure enables biocompatible and multifunctional activity, highlighting AFG as a promising candidate for topical therapy in corneal repair and dry eye management.