Embryologic and fetal development of meibomian glands: Implications in aging and dry eye disease

The meibomian gland (MG) is a specialized sebaceous gland essential for tear film stability and ocular surface health. Age-related meibomian gland dysfunction (ARMGD) is a leading cause of evaporative dry eye disease (DED). The developmental mechanisms governing MG formation and their longterm maintenance are still incompletely understood. This review synthesizes evidence from human and animal studies to define the developmental stages of MG morphogenesis and the key molecular regulators that control gland formation, maturation, and homeostasis. MG development arises from coordinated epithelial-mesenchymal interactions involving FGF, Wnt/βcatenin, EGF, and Hedgehog signaling pathways, together with transcriptional regulators that guide epithelial differentiation and lipid-producing maturation. Parallels with sebaceous gland biology highlight shared regulatory mechanisms, whereas differences in stem cell localization may contribute to tissue-specific susceptibility to aging. Disruption of these developmental and homeostatic pathways is increasingly linked to gland atrophy, altered lipid synthesis, and the pathogenesis of ARMGD. Future studies employing MG organoid models, molecular mechanisms of aging MG, stem/progenitor cell-based approaches, and pathway targeted strategies may help elucidate regenerative mechanisms and lay the groundwork for novel therapeutic interventions for ARMGD.