Ingrid Zahn , Eileen Socher , Antonio Bergua , Thilo Schikorra , Benedikt Kleinsasser , Fabian Garreis , Martin Schicht , Jana Dietrich , Friedrich Paulsen
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引用次数: 0
Abstract
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.
期刊介绍：
Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
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