Taylor Andrew W, Kim Madeleine, Zhao John L, Ng Tat Fong
Department of Ophthalmology, Chobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts, USA.
Ocul Immunol Inflamm. 2025 Jul 22:1-9. doi: 10.1080/09273948.2025.2532821.
The melanocortin pathways are central in maintaining the normal anti-inflammatory microenvironment of the eye. A repository corticotropin injection (RCI) from ANI Pharmaceuticals that activates multiple melanocortin pathways was studied for its effects on experimental autoimmune uveitis (EAU), a murine model of human endogenous uveitis.
At the chronic phase of EAU, the mice received an injection of the RCI. Clinical scoring of the eyes was conducted every 3 to 4 days using fundus microscopy until the uveitis resolved. The eyes were collected, sectioned, and H&E stained for histological scoring. A T-cell reaction assay was performed using spleen cells to measure IFN-g, IL-17, and IL-10 following restimulation with retinal antigen. The effects of the RCI's active pharmaceutical ingredient (API) on LPS-stimulated macrophage production of IL-1β, IL-10, and TNF-α were assessed by ELISA.
The RCI in a dose-dependent manner suppressed the clinical scores of EAU, showing no significant difference in scoring between 400 U/kg of RCI and a group of native α-MSH-treated mice. In parallel, the retinas of the treated mice had a significant decrease in the histology scores. A significant reduction in IFN-γ and IL-17 production was observed in spleen T-cells of the treated EAU mice, with no regulatory immunity to retinal antigens. The API significantly suppressed the production of IL-1β, IL-10, and TNF-α by stimulated macrophages.
RCI treatment effectively suppressed uveitis and protected the retina from inflammatory damage. These findings further illustrate the potential of melanocortin-based therapies for uveitis.
黑皮质素通路在维持眼睛正常的抗炎微环境中起核心作用。研究了ANI制药公司生产的一种能激活多种黑皮质素通路的储存型促肾上腺皮质激素注射液（RCI）对实验性自身免疫性葡萄膜炎（EAU）的影响，EAU是人类内源性葡萄膜炎的小鼠模型。
在EAU的慢性期，给小鼠注射RCI。每隔3至4天使用眼底显微镜对眼睛进行临床评分，直至葡萄膜炎消退。收集眼睛，切片并进行苏木精-伊红（H&E）染色以进行组织学评分。使用脾细胞进行T细胞反应测定，以测量在用视网膜抗原再次刺激后干扰素-γ（IFN-γ）、白细胞介素-17（IL-17）和白细胞介素-10（IL-10）的水平。通过酶联免疫吸附测定（ELISA）评估RCI的活性药物成分（API）对脂多糖（LPS）刺激的巨噬细胞产生白细胞介素-1β（IL-1β）、IL-10和肿瘤坏死因子-α（TNF-α）的影响。
RCI以剂量依赖性方式抑制了EAU的临床评分，400 U/kg的RCI组与一组天然α-促黑素细胞激素（α-MSH）治疗的小鼠在评分上无显著差异。同时，治疗小鼠的视网膜组织学评分显著降低。在治疗的EAU小鼠的脾T细胞中观察到IFN-γ和IL-17的产生显著减少，对视网膜抗原有无调节性免疫。API显著抑制了刺激的巨噬细胞产生IL-1β、IL-10和TNF-α。
RCI治疗有效抑制了葡萄膜炎，并保护视网膜免受炎症损伤。这些发现进一步说明了基于黑皮质素的疗法治疗葡萄膜炎的潜力。
