title: Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.
abstract: The small heat shock protein, αA-crystallin null (αA-/-) 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 αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), 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 αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.
authors.affiliation: Doheny Eye Institute, University of Southern California, Los Angeles, California, United States of America. nrao@usc.edu
authors.forename: Narsing A
authors.initials: NA
authors.lastname: Rao
authors.forename: Sindhu
authors.initials: S
authors.lastname: Saraswathy
authors.forename: Geeta
authors.initials: G
authors.lastname: Pararajasegaram
authors.forename: Suraj P
authors.initials: SP
authors.lastname: Bhat
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D050888:Heat-Shock Proteins, Small / Q000008:administration & dosage*; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014605:Uveitis / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D038202:alpha-Crystallin A Chain / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D050888:Heat-Shock Proteins, Small; D038202:alpha-Crystallin A Chain