Rethinking the pathogenesis of meibomian gland dysfunction: Ductal-centric vs. meibocyte-centric hypothesis

Abstract

Meibomian gland dysfunction (MGD) has traditionally been explained by the ductal-centric hypothesis, which attributes disease progression to ductal obstruction and secondary acinar atrophy. However, this model does not fully account for all clinical and pathological features. Recognizing these limitations, the meibocyte-centric hypothesis has emerged, proposing that intrinsic meibocyte dysfunction and acinar degeneration may play a primary role. In this context, this narrative review incorporates selected original data from animal models to contrast the ductal-centric and meibocyte-centric hypotheses, and synthesizes current concepts of MGD pathogenesis through a comprehensive literature review. In particular, two models illustrated how ductal blockage and meibocyte injury differentially affect gland morphology. Experimental findings supporting the ductal-centric hypothesis include ductal obstruction and orifice blockage leading to secondary acinar degeneration. Observations such as gland dropout without obstruction and lid margin dimpling are not fully explained by this model. In contrast, experimental studies demonstrate that meibocyte damage leads to gland dysfunction without ductal dilatation, highlighting intrinsic cellular pathology as a complementary driver to the traditional obstruction model. In addition, immune-mediated processes are increasingly recognized as a distinct pathogenic axis that interacts with both ductal and acinar pathways. This evolving perspective carries important therapeutic implications, as current ductal-focused treatments may be insufficient to address acinar pathology. Future approaches should target both ductal and acinar compartments, with emphasis on restoring meibocyte function, modulating immune pathways, and promoting glandular regeneration.

Keywords: Ductal-centric hypothesis; Immune-mediated pathogenesis; Meibocyte-centric hypothesis; Meibomian gland dysfunction.