Zahn Ingrid, Socher Eileen, Bergua Antonio, Schikorra Thilo, Kleinsasser Benedikt, Garreis Fabian, Schicht Martin, Dietrich Jana, Paulsen Friedrich
Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Biomed Pharmacother. 2025 Apr;185:117937. doi: 10.1016/j.biopha.2025.117937. Epub 2025 Mar 2.
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.
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.
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.
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.
睑板腺分泌富含脂质的物质，形成泪膜的表层，防止过度蒸发。这些腺体功能障碍（睑板腺功能障碍，MGD）是干眼病（DED）的主要原因，干眼病日益引起公众健康关注。目前，针对干眼病的药物治疗有限。然而，α/β-黑素细胞刺激激素（α/β-MSH）作为黑素皮质素受体（MCR）的配体，已知可调节皮脂腺的脂肪生成和分化。本研究调查了α/β-MSH对人睑板腺外分泌的影响。
对人睑板腺和永生化人睑板腺上皮细胞系（ihMGECs）进行MCR表达的免疫组织化学和逆转录聚合酶链反应（RT-PCR）。使用油红O染色、透射电子显微镜、定量聚合酶链反应（qPCR）和环磷酸腺苷（cAMP）检测分析α/β-MSH（激动剂）和JNJ-10229570（拮抗剂）对ihMGECs脂质生成和MCR反应的影响。此外，研究了α/β-MSH对人眼睑离体器官型切片培养（OSC）的影响。
在人睑板腺中证实了MCR的表达。用α/β-MSH刺激可提高cAMP水平并增加MCR表达。α/β-MSH在ihMGECs和OSC中剂量依赖性地诱导脂质生成，导致脂质小滴形成增加和脂肪生成标志物上调。联合使用JNJ-10229570可抑制此效应。
我们的数据首次表明人睑板腺表达MCR，并且MCR的刺激/抑制会改变cAMP反应、MCR表达和脂肪生成标志物，从而影响睑脂的生成。因此，α/β-MSH对睑脂生成有积极影响，在MGD腺体分泌变化及潜在治疗的背景下应予以考虑。
