A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis

Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon alpha1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNalpha-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNalpha-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFalpha were suppressed when IFNalpha-C was simultaneously present. TNF-alpha mediated induction of NF-kappaB and signaling by IL-17A were attenuated by IFNalpha-C. Differentiated ARPE-19 cells were treated with TNFalpha in the presence or absence IFNalpha-C and analyzed by immmunhistochemistry. IFNalpha-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFalpha was prevented by IFNalpha-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNalpha-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNalpha-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigen-specific T cell proliferation that was inhibited in the presence of IFNalpha-C. IFNalpha-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.