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S. Saraswathy, N. A. Rao; Protective and Therapeutic Role of A Crystallin in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5237.
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© ARVO (1962-2015); The Authors (2016-present)
αA crystallin is selectively upregulated in the photoreceptors in early phase of experimental autoimmune uveitis (EAU) and prevents photoreceptor apoptosis from mitochondrial oxidative stress and inflammatory infiltration. We investigated the mechanism of anti-inflammatory and protective role of this protein in EAU.
αA-/- and corresponding wild type (WT) mice were immunized with IRBP peptide. The αA-/- mice with EAU were treated with αA crystallin recombinant protein (10µg) or saline intravenously from day 7 post immunization (p.i) and eyes enucleated on day 14 (p.i) for histological analysis. A second group of αA-/- , WT and group of αA-/- mice treated with αA crystallin were sacrificed on day 21. Retinas were submitted to real time PCR to detect the gene expression of Th1/Th2/Th17 cytokines and its protein expression was assayed by MultiAnalyte Elisarray kit. Adoptive transfer was performed by injecting IRBP-reactive splenocytes/lymph node cells from a third group of αA -/- and WT mice to Rag2-/- mice. TUNEL assay was performed on a fourth group of WT with EAU treated with Saline, αA , αB and γ crystallin on day 21 p.i.
The αA-/- mice showed more severe inflammation compared to the WT whereas in the αA crystallin treatment group there was no inflammation. The gene and protein expression of T cell cytokines increased in compared to WT with EAU. αA treatment significantly reduced the cytokine levels in the αA-/- mice. Significantly worse disease was observed in Rag2-/- recipient mice with αA -/- cells compared to the WT. Large numbers of TUNEL positive cells were found in the WT mice with EAU treated with saline, αB and γ crystallin whereas few cells were detected in αA crystallin treated mice.
The amelioration of disease in αA crystallin treated mice may be due to decreased infiltration of immune cells into the retina and suppression of immune cell function during EAU. αA crystallin also play an important role in preventing apoptosis of the photoreceptors during EAU. Thus systemic αA crystallin treatment offers a unique approach for preventing photoreceptor apoptosis in uveitis and other blinding diseases.
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