0.005% Preservative-Free Latanoprost Triggers Meibomian Gland Dysfunction in Mice via Inflammation and Oxidative Stress Modulation

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 for periods ranging from 7 to 28 days. Morphological changes of the meibomian gland in mice were detected by immunohistochemistry. Immunofluorescence staining, western blotting, and/or quantitative real-time fluorescence quantitative PCR (qRT-PCR) were used to examine the expression levels of prostaglandin F2α receptor (FP), inflammatory cells and mediators, oxidative stress and signaling pathways 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 such as CCL2, IL-1β, TNF-α, IL-6, and CXCL5 showed elevated expression levels. Notably, there was an increase in oxidative stress proteins, including NOX4, 3-NT, and 4-HNE, along with a decrease in the expression of antioxidant stress proteins, including SOD2 and Keap-1. 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.