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bioRxiv · 10.1101/2019.12.23.886986

A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis

Ahmed, C. M.·Ildefonso, C. J.·Johnson, H. M.·Lewin, A. S.
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Abstract

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 1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFN-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFN-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNF were suppressed when IFN-C was simultaneously present. TNF- mediated induction of NF-kB and signaling by IL-17A were attenuated by IFN-C. Differentiated ARPE-19 cells were treated with TNF in the presence or absence IFN-C and analyzed by immmunhistochemistry. IFN-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNF was prevented by IFN-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFN-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFN-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigenspecific T cell proliferation that was inhibited in the presence of IFN-C. IFN-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.

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Ahmed, C. M., Ildefonso, C. J., Johnson, H. M., Lewin, A. S.. 2019-12-23. A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis. https://doi.org/10.1101/2019.12.23.886986

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