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U. C. Yadav, S. K. Srivastava, K. V. Ramana; Amelioration of Experimental Autoimmune-Induced Uveitis by Aldose Reductase Inhibition in Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4826.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the efficacy of aldose reductase (AR) inhibitors in the prevention of experimental autoimmune-induced uveitis (EAU) in rats, and cytotoxic signals induced by lipopolysaccharide (LPS) in human non-pigmented ciliary epithelial (NPE) cells.
The Lewis rats were immunized with bovine interphotoreceptor retinoid-binding protein (bIRPB) peptide 1169-1191 to develop EAU. Two days after immunization, AR inhibitor, Fidarestat, was administered (7 mg/Kg body wt /day; i.p.). The rats were killed 14 days after the immunization and aqueous humor (AqH) was collected. The protein concentration and the levels of inflammatory markers were determined in AqH. Immunohistochemical analysis of eye sections was performed to determine the expression of inflammatory markers, ROS and NF-ΚB, and the effect of AR inhibition on immune response was investigated in isolated T-lymphocytes. The NPE cells were stimulated with LPS, and the levels of NO, PGE2 were measured by ELISA kits. Immunobloting was performed to measure protein kinases and inflammatory markers.
EAU caused severe infiltration of leukocytes in the posterior as well as anterior chambers of the eye. Increase in the concentration of proteins, inflammatory cytokines and chemokines in rat AqH, expression of inflammatory marker proteins, and NF-ΚB in ciliary body and retina of rat eyes were significantly prevented by AR inhibition. Increased proliferation of T cells from EAU rats in response to bIRBP was significantly prevented by AR inhibition. In NPE cells, AR inhibition prevented LPS-induced apoptosis and activation of MAPK/JNK/NF-kB/AP1 pathway and generation of PGE2 and NO.
Our results suggest that AR inhibition can prevent autoimmune-induced inflammatory signals leading to uveitis in rats; therefore inhibition of AR could be a novel therapeutic approach to ameliorate ocular inflammatory complications such as uveitis.
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