Abstract
Purpose :
The meibomian glands are specialized sebaceous glands and produce a lipid-rich secretion called meibum. Once released, it forms the superficial layer of the tear film and prevents excessive evaporation. Dysfunction of the meibomian glands (MGD) is the main cause of dry eye disease (DED), which is an ever-increasing public health problem. To date, there are only few pharmacological options for the treatment of DED. However, α-/β- melanocyte-stimulating hormones (α-/β-MSH), ligands of the melanocortin receptors (MCR), are known to regulate lipid production and differentiation in the sebaceous glands. Therefore, we investigated in this experimental study the influence of α-/β-MSH on exocrine secretion in meibomian glands.
Methods :
Immunohistochemistry and RT-PCR was performed to verify MCR expression in human meibomian (N=4) glands and an immortalized human meibomian gland epithelial cell line (ihMGECs) (N=4). ihMGECs in proliferating and differentiated states were stimulated with α/β-MSH (MCR agonists) and JNJ-10229570 (MCR antagonist). The effects of α/β-MSH on lipid production and the response via MCRs (G protein-coupled receptors) were analyzed by Oil Red O (ORO) staining and cAMP assay (N=8). Western Blot analysis and qPCR (N=8) were performed to investigate the effects of α/β-MSH on protein and gene expression levels of MCRs and lipogenesis markers.
Results :
The expression of MCRs was verified in human meibomian glands. Stimulation with both α- and β-MSH induce cAMP and lipid production in a dose-dependent way (p<0.001), whereas this effect was significant reduced with the simultaneously incubation of the MCR antagonist (p=0.005). The gene expression of stearoyl-CoA desaturase (p=0.0204), fatty acid-binding protein 4 (p=0.0261) and peroxisome proliferator-activated receptor gamma (p=0.0064), was significant increased after α and/or β-MSH treatment. Likewise, α and/or β-MSH significantly increased gene expression of MCRs (p=0.0437), while simultaneous treatment with an MCR antagonist inhibited the effect on both lipogenesis markers and MCRs.
Conclusions :
Our data show for the first time that human meibomian glands express MCRs and that stimulation/inhibition of MCRs alters the expression of MCRs and lipogenesis markers and thus genesis of meibum. Therefore, it is likely that α-/β-MSH positively affects meibum production and should be considered regarding changes in glandular secretion in MGD and potential treatments.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.