Maresin 1 Ameliorates Blue Light Overexposure-Induced Meibomian Gland Dysfunction via Inhibition of NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis.

PURPOSE: Blue light emitted from digital screens represents a significant environmental factor contributing to computer vision syndrome-related ocular surface damage. This study aimed to investigate the protective effects of maresin 1 (MaR1), a specialized proresolving lipid mediator derived from docosahexaenoic acid, in meibomian gland dysfunction (MGD) induced by blue light overexposure in both in vivo and in vitro experiments. METHODS: In vivo, male Sprague-Dawley rats were exposed to blue light for 1 month to induce MGD. After 14 days of MaR1 or PBS eye drop treatment, corneal fluorescein staining and inflammatory cytokine expression were evaluated. Lipid secretion and ductal keratinization were assessed using Nile red and keratin 1 staining. In vitro, pyroptosis was induced in primary rat meibomian gland epithelial cells (PRMGECs) by lipopolysaccharide and ATP stimulation, and pyroptosis-related protein expression was analyzed by immunofluorescence and Western blot analysis. RESULTS: Excessive blue light exposure induced MGD-like clinical signs, characterized by extensive corneal fluorescein staining, obstruction of MG ducts, and a reduction in total glandular area in rats. Moreover, these ocular surface injuries were accompanied by the upregulation of IL-1β and IL-18 levels and the activation of NLRP3/caspase 1/GSDMD-mediated pyroptosis. Following MaR1 treatment, inflammatory cell infiltration was alleviated, the lipid secretion function of the meibomian glands was restored, and ductal hyperkeratinization was suppressed. In vitro, MaR1 significantly inhibited pyroptosis-related protein expression in the PRMGEC pyroptosis model. CONCLUSIONS: Our study indicated that MaR1 alleviated blue light-induced MGD by inhibiting NLRP3/caspase 1/GSDMD-mediated pyroptosis. This finding provides a novel therapeutic perspective for the treatment of environment-related dry eye disease.