Purchase this article with an account.
S. Saraswathy, M. Na, G.S. Wu, N.A. Rao; Mechanism of Oxidative Stress During Early Experimental Autoimmune Uveitis Prior to Leukocyte Infiltration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2086.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have previously demonstrated peroxynitrite–mediated oxidative stress in photoreceptors during early experimental autoimmune uveitis (EAU) prior to leukocyte infiltration. In this study we have investigated the mechanism of stress during the initial phase of uveitis prior to inflammatory cell infiltration.
Experimental autoimmune uveitis was induced in Lewis rats with S–antigen and the changes in gene expression of the cytokines and chemokines on post–immunization days 0, 5, 8, 11, and 14 were evaluated by quantitative real–time PCR. The protein expression levels of MCP–1 at days 0, 5, 8, 11, and 14 were studied in the retina by immunohistochemistry and western blot analysis. Macrophage and leukocyte infiltration on these days were also studied by looking at the expression of ED1 and CD45.
Among the cytokines studied, the gene expression of iNOS, TNF–α and IFN– was significantly (p<0.05) increased during initial phase of EAU at post–immunization day 5; however, there was no evidence of leukocyte or macrophage infiltration until day 8. Other cytokines were significantly upregulated (p<0.05) only from day 8 onwards, and peaked at day 14. The mRNA expression of MCP–1 and MIP–1α, however, did not indicate any notable changes during the early phase, but began to show a significant increase from day 8 with a peak at day 14. Immunohistochemical and western blot analysis of MCP–1 validated the PCR results.
During the initial phase of uveitis, TNF–α and IFN– are upregulated prior to inflammatory cell infiltration, which appears to upregulate iNOS, thereby resulting in subsequent oxidative stress. Oxidative stress appears to be an initial event leading to the amplification of inflammation, resulting in both clinical and histologic expression of uveitis in the form of inflammatory cell infiltration. However, the immune mechanism that drives cytokine expression is not clear.
This PDF is available to Subscribers Only