Analysis of Serum microRNAs During the Development of Experimental Autoimmune Uveoretinitis in Rats

Purpose: To investigate alterations in circulating microRNAs (miRNAs) in the development of experimental autoimmune uveoretinitis (EAU) in rats. Methods: Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide (R14) and EAU clinical scores were assessed on day 0 (baseline), and days 7, 14, and 21 after immunization. Total RNA was isolated from serum at the same timepoints and used for microarray analysis. Results: The clinical score of EAU peaked on day 14 and decreased on day 21. Hierarchical cluster analysis and principal component analysis (PCA) of serum miRNA expression displayed distinctly different miRNA profiles between baseline and days 7, 14, and 21 after immunization. Microarray analysis revealed significantly increased expression of 5 (day 7), 9 (day 14), and 10 (day 21) miRNAs, and significantly decreased expression of 19 (day 7), 20 (day 14), and 19 (day 21) miRNAs compared to baseline. Of note, the expression of miRNA-146a-5p, known to be involved in EAU, and miRNA-150-5p was significantly elevated on days 14 and 21. Bioinformatics analysis revealed that mucin type O-glycan biosynthesis and cell adhesion molecules were major pathways affected during the development of EAU. Conclusions: Hierarchical cluster analysis and PCA showed distinctly different miRNA profiles at baseline versus after IRBP immunization. Upregulation of serum miRNA-146a-5p and miRNA-150-5p was observed in the effector and resolution phases of EAU. Analysis of circulating miRNAs may help to delineate systemic epigenetic changes occurring in the development of EAU, and may lead to new insights in our understanding of human uveitis.