Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA.
Ocul Immunol Inflamm. 2022 May 19;30(4):876-886. doi: 10.1080/09273948.2020.1849735. Epub 2021 Feb 22.
The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoimmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of phagolysosome-activation in macrophages following α-MSH-treatment of EAU.
The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(-/-) mice were used to treat macrophages to assay for phagolysosome activation.
MC5r(-/-) mice treated with α-MSH recovered from EAU, but with greater retinal damage, and the RPE suppressed phagolysosome activation in wild type but not in MC5r(-/-) macrophages. In addition, α-MSH did not suppress phagolysosome activation in MC5r(-/-) macrophages, and resting-MC5r(-/-) macrophages had augmented phagocytic activity.
α-MSH treatment of EAU mediates a MC5r-dependent recovery of RPE suppression of phagolysosome activation in macrophages possibly altering antigen processing and presentation. Also, MC5r-expression helps protect the retina from inflammatory damage. In addition, MC5r-expression is important in the homeostatic maintenance of phagosome-maturation within macrophages.
RPE-神经肽 α-MSH 的治疗用途可抑制实验性自身免疫性葡萄膜炎（EAU）。这种抑制作用部分是通过 α-MSH 黑素皮质素 5 受体（MC5r）实现的。因此，我们研究了 MC5r 表达在 RPE 抑制吞噬体激活中的可能作用，在 EAU 经 α-MSH 治疗后，这种抑制作用会恢复。
用经 α-MSH 处理的 EAU 野生型和 MC5r（-/-）小鼠原位培养 RPE-眼球杯的条件培养基处理巨噬细胞，以检测吞噬体激活。
用 α-MSH 处理的 MC5r（-/-）小鼠从 EAU 中恢复，但视网膜损伤更大，而 RPE 抑制了野生型但不抑制 MC5r（-/-）巨噬细胞中的吞噬体激活。此外，α-MSH 不能抑制 MC5r（-/-）巨噬细胞中的吞噬体激活，而静止状态的 MC5r（-/-）巨噬细胞具有增强的吞噬活性。
α-MSH 治疗 EAU 介导了 MC5r 依赖性的 RPE 抑制吞噬体激活的恢复，可能改变了抗原加工和呈递。此外，MC5r 表达有助于保护视网膜免受炎症损伤。此外，MC5r 表达对于巨噬细胞中吞噬体成熟的动态平衡维持很重要。
