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

IF 2.6 4区医学 Q2 OPHTHALMOLOGY

Ocular Immunology and Inflammation Pub Date : 2025-04-23 DOI:10.1080/09273948.2025.2483430

Shoko Saito, Hiroshi Keino, Ichiro Takasaki, Takayo Watanabe, Annabelle A Okada

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引用次数: 0

Abstract

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.

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大鼠实验性自身免疫性葡萄膜视网膜炎发生过程中血清microrna的分析。

目的：探讨大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）发生过程中循环microRNAs （miRNAs）的变化。方法：采用IRBP肽（R14）免疫Lewis大鼠，分别于免疫后第0天（基线）、第7天、第14天、第21天评价EAU临床评分。在同一时间点从血清中分离总RNA并用于微阵列分析。结果：EAU临床评分在第14天达到高峰，第21天下降。血清miRNA表达的层次聚类分析和主成分分析（PCA）显示，基线与免疫后第7、14和21天的miRNA表达谱存在明显差异。微阵列分析显示，与基线相比，5（第7天）、9（第14天）和10（第21天）mirna的表达显著增加，19（第7天）、20（第14天）和19（第21天）mirna的表达显著降低。值得注意的是，已知参与EAU的miRNA-146a-5p和miRNA-150-5p的表达在第14天和第21天显著升高。生物信息学分析表明，粘蛋白型o -聚糖的生物合成和细胞粘附分子是EAU发育过程中受影响的主要途径。结论：层次聚类分析和PCA显示基线时与IRBP免疫后miRNA谱明显不同。血清miRNA-146a-5p和miRNA-150-5p在EAU的作用期和溶解期均出现上调。对循环mirna的分析可能有助于描述EAU发展过程中发生的系统性表观遗传变化，并可能为我们对人类葡萄膜炎的理解提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ocular Immunology and Inflammation 医学-眼科学

CiteScore

6.20

自引率

15.20%

发文量

285

审稿时长

6-12 weeks

期刊介绍： Ocular Immunology & Inflammation ranks 18 out of 59 in the Ophthalmology Category.Ocular Immunology and Inflammation is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and vision scientists. Published bimonthly, the journal provides an international medium for basic and clinical research reports on the ocular inflammatory response and its control by the immune system. The journal publishes original research papers, case reports, reviews, letters to the editor, meeting abstracts, and invited editorials.