Pharmacologic Alteration of Meibum Lipid Composition Alleviates Dry Eye Phenotype in Awat2-/- Mice

Meibomian glands (MGs) produce lipids that stabilize the tear film and maintain ocular surface homeostasis. Dysfunction of MG lipid secretion is a major cause of evaporative dry eye (EDE). The purpose of this study was to test whether pharmacologic modulation of meibum lipid biosynthesis could improve the physicochemical properties of meibum and thereby slow the progression of EDE in a mouse model of the disease.

Awat2-/- mice, an animal model of EDE, were treated systemically with ATR101 (nevanimibe), a selective sterol O-acyltransferase 1 (SOAT1) inhibitor that suppresses cholesteryl ester (CE) synthesis. Meibum lipid composition, MG morphology, tear film breakup time, and corneal integrity were analyzed and compared with untreated controls to monitor disease progression.

Pharmacologic intervention in the CE biosynthesis in Awat2-/- mice altered the physicochemical properties of meibum, decreasing its melting temperature and increasing lipid fluidity. Treated mice exhibited reduced MG ductal obstruction and preservation of MG morphology. These changes were accompanied by prolonged tear film breakup time, improved tear film stability, and preserved corneal integrity compared with untreated Awat2-/- mice.

Pharmacologic intervention in meibogenesis corrects a pathogenic lipid imbalance in Awat2-deficient MGs and improves tear film and MG function. These findings identify lipid metabolic remodeling of meibum as a mechanistically grounded therapeutic strategy for obstructive MG dysfunction and evaporative dry eye.