Abstract
PURPOSE: 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. METHODS: 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. RESULT: 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. CONCLUSIONS: RCI treatment effectively suppressed uveitis and protected the retina from inflammatory damage. These findings further illustrate the potential of melanocortin-based therapies for uveitis.