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Immunology - Ophthalmology - Physiology

Small Heat Shock Protein aA-Crystallin Prevents Photoreceptor Degeneration in Experimental Autoimmune Uveitis
Published: Friday, March 30, 2012
Author: Narsing A. Rao et al.

by Narsing A. Rao, Sindhu Saraswathy, Geeta Pararajasegaram, Suraj P. Bhat

The small heat shock protein, aA-crystallin null (aA-/-) 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 aA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only aA and not aB-crystallin (aB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of aA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing aA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that aA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that aA administration causes marked reduction in Th1 cytokines (TNF-a, IL-12 and IFN-?), 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 aA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.