A Novel Rat Model for Human Meibomian Gland Dysfunction and Ocular Rosacea.

Abstract

PURPOSE: Ocular rosacea (OR) is a 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 models. This study aimed to develop a rat model of MGD and OR, and validate its relevance by comparing with the human pathology. METHODS: Rat upper eyelids were exposed to UVB (300 mJ/cm2/day) for 5 days. Clinical signs, Meibomian gland (MG) morphology, and function were assessed and compared with human OR samples. Transcriptomics and lipidomics were performed to investigate UVB-induced changes. RESULTS: UVB caused acute damage to eyelid skin and MGs with increased oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and elevated lipid production. Whereas inflammation and lipid hyperproduction decreased during the 2-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 patients with OR, suggesting chronic and irreversible damage to MGs. Transcriptomic analysis showed shared gene regulation patterns between UVB-induced rat MGs and human rosacea and MGD. Lipidomic analysis revealed UVB-induced changes in MG lipid composition. CONCLUSIONS: 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.