Preservative-free latanoprost induces meibomian gland dysfunction through inflammatory and oxidative stress pathways.

PURPOSE: This study aimed to investigate the effects of preservative-free latanoprost on meibomian gland function in mice and its possible mechanism. METHODS: Disproportionality analysis was conducted using the FAERS database to evaluate adverse reaction reports and epidemiological characteristics associated with preservative-free latanoprost. In mouse models, 0.005% preservative-free latanoprost or vehicle control was topically applied four times daily for 7, 14, or 28 days. Morphological changes of the meibomian gland in mice were detected by immunohistochemistry. Immunofluorescence staining, western blotting, and quantitative real-time PCR (qRT-PCR) were used to assess the expression of the prostaglandin F2α receptor (FP), inflammatory cells and mediators, oxidative stress-related markers, and signaling pathway–related factors in mouse meibomian gland tissues. RESULTS: Reports of adverse reactions caused by preservative-free latanoprost increased annually in the FAERS database. Locally applied preservative-free latanoprost in mice led to an escalation of mucous secretion at the eyelid margin, accompanied by meibomian gland duct obstruction, lipid accumulation in glandular acini, an elevation in the expression levels of FP and Slco2a, and a reduction in the expression levels of PGDH within the meibomian glands. Other inflammatory markers, including CCL2, IL-1β, TNF-α, IL-6, and CXCL5, were significantly upregulated in the latanoprost-treated group, showing approximately 1.3–1.5-fold increases in CCL2, IL-1β, TNF-α, and CXCL5, and a more pronounced ~4-fold increase in IL-6 (p < 0.05). Consistently, oxidative stress-related proteins NOX4, 3-nitrotyrosine (3-NT), and 4-hydroxynonenal (4-HNE) were significantly increased (~1.3–1.5-fold, p < 0.05), whereas the antioxidant proteins superoxide dismutase 2 (SOD2) and Keap-1 were significantly altered, with SOD2 decreased to ~0.6-fold and Keap-1 increased to ~1.2-fold compared with controls (p < 0.05). Additionally, the Erk and NF-κB signaling pathways were significantly activated. CONCLUSION: 0.005% preservative-free latanoprost induces meibomian gland dysfunction in mice by promoting inflammatory responses and oxidative stress. CLINICAL TRIAL NUMBER: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40360-025-01078-9.