Attenuation of experimental autoimmune uveoretinitis in mice by IKK beta inhibitor IMD-0354

摘要

Uveitis is a sight-threatening intraocular inflammatory disease that accounts for almost 10% of blindness worldwide. NF-kappa B signaling plays pivotal roles in inflammatory diseases. We have reported that IMD-0354, which inhibits NF-kappa B signaling via selective blockade of IKK-beta, suppresses inflammation in several ocular disease models. Here, we examined the therapeutic effect of IMD-0354 in an experimental autoimmune uveoretinitis (EAU) model, a well-established animal model for endogenous uveitis in humans. Systemic administration of IMD-0354 significantly suppressed the clinical and histological severity, inflammatory edema, and the translocation of NF-kappa B p65 into the nucleus of retinas in EAU mice. Furthermore, IMD-0354 treatment significantly inhibited the levels of several Th1 /Th17-mediated pro-inflammatory cytokines in vitro. Our current data demonstrate that inhibition of IKK beta with IMD-0354 ameliorates inflammatory responses in the mouse EAU model, suggesting that IMD-0354 may be a promising therapeutic agent for human endogenous uveitis. (C) 2020 Published by Elsevier Inc.