Alpha- and beta-melanocyte stimulating hormone positively impact lipogenesis of meibomian gland cells in vitro and ex vivo

Purpose

The meibomian glands produce a lipid-rich secretion that forms the superficial layer of the tear film, preventing excessive evaporation. Dysfunction of these glands (MGD) is the primary cause of dry eye disease (DED), a growing public health concern. Currently, there are limited pharmacological treatments for DED. However, α-/β-melanocyte-stimulating hormones (α-/β-MSH), ligands of the melanocortin receptors (MCR), are known to regulate lipogenesis and differentiation in sebaceous glands. This study investigated the influence of α-/β-MSH on exocrine secretion in human meibomian glands.

Methods

Immunohistochemistry and RT-PCR for MCR expression were performed in human meibomian glands and an immortalized human meibomian gland epithelial cell line (ihMGECs). The effects of α-/β-MSH (agonists) and JNJ-10229570 (antagonist) in ihMGECs on lipid production and MCR response were analyzed using Oil-Red-O staining, transmission electron microscopy, qPCR, and a cAMP assay. Additionally, the effect of α-/β-MSH on an ex vivo organotypic slice culture (OSC) of human eyelids was investigated.

Results

MCR expression was confirmed in human meibomian glands. Stimulation with α-/β-MSH increased cAMP levels and MCR expression. α-/β-MSH dose-dependently induced lipid production in ihMGECs and OSC, resulting in increased lipid droplet formation and upregulation of lipogenesis markers. Co-administration of JNJ-10229570 suppressed this effect.

Conclusion

Our data show for the first time that human meibomian glands express MCRs and that stimulation/inhibition of MCRs alters cAMP response, MCR expression, and lipogenesis markers, thereby affecting the genesis of meibum. Therefore, α-/β-MSH positively impacts meibum production and should be considered in the context of changes in glandular secretion in MGD and potential treatments.