Injection of an alpha-melanocyte stimulating hormone expression plasmid is effective in suppressing experimental autoimmune uveitis

PurposeThe neuropeptide, alpha-melanocyte stimulating hormone (α-MSH), is an endogenous antagonist of inflammation. Injections of α-MSH peptide into inflamed tissues have been found to be very effective in suppressing autoimmune and endotoxin mediated diseases. We evaluated the potential to suppress ocular autoimmune disease (uveitis) by augmenting the expression of α-MSH through subconjunctival injections of naked adrenocorticotropic hormone amino acids 1–17 (ACTH1–17) plasmid.MethodsWe clinically scored the uveitis over time in B10.RIII, C57BL/6, and melanocortin 5 receptor knock-out (MC5r(−/−)) mice with experimental autoimmune uveitis (EAU) that were conjunctively injected with a naked DNA plasmid encoding ACTH1–17 at the time of EAU onset and three days later. The post-EAU retina histology of plasmid injected eyes was examined, and post-EAU concentrations of α-MSH in aqueous humor was assayed by ELISA.ResultsThe subconjunctival injection of ACTH1–17 plasmid augmented the concentration of α-MSH in the aqueous humor of all post-EAU mice. The injection of ACTH1–17 suppressed the severity of EAU in the B10.RIII and C57BL/6 mice but the MC5r(−/−) mice. In all the models of EAU, the ACTH1–17 injection helped to preserve the structural integrity of the retina; however, post-EAU aqueous humor was not immunosuppressive.ConclusionsThe subconjunctival injection of the α-MSH expression vector ACTH1–17 plasmid is effective in suppressing EAU. The suppressive activity is dependent on MC5r expression, and possibly works though α-MSH antagonism of inflammation than on α-MSH directly modulating immune cells. The results suggest that an effective therapy for uveitis could include a gene therapy approach based on delivering α-MSH.