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N. Hashida, N. Ohguro, S. Hohki, Y. Saishin, Y. Tano; Expression Analysis of Cytokine and Chemokine Genes During Development and Remission of Murine Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2648.
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© ARVO (1962-2015); The Authors (2016-present)
The aim of this study was to investigate sequential expression changes in cytokines and chemokines and their receptors during development and remission of murine experimental autoimmune uveoretinitis (EAU).
C57BL/6 mice were immunized with human interphotoreceptor retinoid-binding protein peptides to induce EAU. From immunization to 30 days after immunization, RNA was isolated daily from the eyes of EAU mice. For gene expression analysis, dynamic changes in gene expression during the pathogenesis of EAU were analyzed by TaqMan Gene Expression Assay (Low Density Array) that contained most chemokines/cytokines and their receptors (96 genes), using beta-actin as the endogenous control. Data comparisons between EAU mice and normal control mice were performed. Gene clusters based on the expression profiles were analyzed to determine the candidate genes for the pathogenesis of inflammation.
The expression of the genes encoding chemokines/cytokines dramatically changed from the start of immunization. Among the selected 96 genes in Low Density Array, 93 genes had detectable expression levels at least one observation point. Hierarchical cluster analysis from the selected quantitative reverse transcriptase-polymerase chain reaction results showed that gene expression during development and remission of EAU was classified into five clustering patterns and also discriminated four distinct changes during daily expression (early, intermediate, active, and remission phases). Gene expressional changes in the active phase of EAU showed biphasic patterns: up-regulation of genes including IFN-gamma and CXCL 9 at the peak of inflammation (from 16-18 days after peptide inoculation) and transient overexpression of several genes at 20 days.
Dynamic expression changes of cytokine and chemokine genes could be involved in the development and the remission of EAU. Clustering analysis of comprehensive gene expression during the natural course of EAU may provide novel therapeutic targets to control ocular inflammation.
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