Small Heat Shock Protein αA-Crystallin Prevents Photoreceptor Degeneration in Experimental Autoimmune Uveitis

The small heat shock protein, alpha A-crystallin null (alpha A(-/-)) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of alpha A preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only alpha A and not alpha B-crystallin (alpha B), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of alpha A in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing alpha A(-/-) and wild type mice with EAU as donors and Rag2(-/-) as the recipient mice), which indicate that alpha A protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that alpha A administration causes marked reduction in Th1 cytokines (TNF-alpha, IL-12 and IFN-gamma), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that alpha A protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.