Zhu, L.; Rodrigues-Braz, D.; Gelize, E.; Crepin, M.; Peltier, C.; Lheure, C.; Morel, X.; Bourges, J.-L.; Berdeaux, O.; Behar-Cohen, f.; ZHAO, M.

Ocular Rosacea (OR) is a common chronic inflammatory and vision-threatening disease of the ocular surface often associated with Meibomian gland dysfunction (MGD). Despite its clinical impact, OR remains underdiagnosed and incurable. The pathogenesis of OR and MGD is poorly understood, partly due to a lack of reliable experimental models. This study described the development of a new rat model of MGD and OR, and validated its relevance by comparing with the human pathology. Targeted exposure of rat eyelid to UVB, a known triggering factor for rosacea, caused acute damage to eyelid skin and MGs with increased oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and elevated lipid production. While inflammation and lipid hyperproduction decreased during the two-week healing process, MG duct hyperkeratinization and meibocyte stem cell depletion persisted, leading to MGD and corneal epithelial defects. Progressive fibrosis in rat MGs was similar to that observed in human OR patients, suggesting chronic and irreversible damage to MGs. Transcriptomic intersection analysis showed overlapping gene regulation patterns between UVB-exposed rat MGs and human rosacea and MGD. Lipidomic analysis revealed UVB-induced changes in MG lipid composition, paralleling human MGD. This model is a valuable tool for studying the pathophysiology of MGD in OR and evaluating new treatments. The transcriptomic and lipidomic similarities between rat model and human disease provide insights into shared molecular pathways and lipid composition, offering potential biomarkers for diagnosis and therapeutic targets.