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Noriyasu Hashida, Kohji Nishida; Expression Analysis Of Microrna During Development Of Murine Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2950.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate sequential expression changes in microRNA (miRNA) during the natural course of murine experimental autoimmune uveoretinitis (EAU).
C57BL/6 mice were immunized with human interphotoreceptor retinoid-binding protein peptides 1-20 to induce EAU. From immunization to day 30, RNA was isolated at 5-day intervals from the eyes of EAU mice. For gene expression analysis, dynamic changes in miRNA expression during EAU pathogenesis were analyzed using TaqMan. The Array MicroRNA Card that contains most miRNAs (641 genes) was used; snoRNA202 was the endogenous control. Data were compared between the peptide-injected group and the placebo-injected group. Gene clusters based on expression profiles were analyzed to determine candidate miRNA that participated in the pathogenesis of inflammation.
The expression of most miRNAs changed dramatically from the start of immunization; 295 of the 641 miRNAs analyzed had significant expression changes. Hierarchical cluster analysis of the selected quantitative reverse transcriptase-polymerase chain reaction results showed that gene expression in the natural course of EAU was classified into four patterns of clusters. To search for miRNA that might regulate the inflammatory genes, we examined the potential target genes that might control ocular inflammation in EAU. Down-regulated miR-381 expression, a candidate regulator of the NF-kappaB inhibitor, occurred on days 10 and 15. Up-regulation of let-7a expression, a regulator of IL-10, occurred on days 25 and 30.
Dynamic expression changes in miRNAs may be involved in EAU pathogenesis. Our results suggest that changes in the expression levels of specific miRNAs and their candidate target genes are involved in development and remission of EAU.
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