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Updated: May 8, 2025
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Analysis of Serum microRNAs During the Development of Experimental Autoimmune Uveoretinitis in Rats
Shoko Saito1, Hiroshi Keino1, Ichiro Takasaki2
1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
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.
Insights
Circulating microRNAs (miRNAs) show distinct profiles during experimental autoimmune uveoretinitis (EAU) development. Upregulation of specific miRNAs, like miRNA-146a-5p, offers insights into uveitis pathogenesis.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Experimental autoimmune uveoretinitis (EAU) is an animal model for human uveitis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- Alterations in circulating miRNAs may reflect systemic changes during autoimmune diseases.
Purpose of the Study:
- To investigate changes in circulating microRNAs (miRNAs) during the development of experimental autoimmune uveoretinitis (EAU) in rats.
- To identify potential miRNA biomarkers for EAU.
Main Methods:
- Lewis rats were immunized to induce EAU.
- Serum samples were collected at multiple time points post-immunization.
- Microarray analysis was performed to profile serum miRNA expression.
- Bioinformatics analysis identified affected pathways.
Main Results:
- EAU clinical scores peaked on day 14.
- Serum miRNA profiles differed significantly between baseline and EAU development.
- Several miRNAs were found to be significantly upregulated or downregulated.
- miRNA-146a-5p and miRNA-150-5p showed increased expression during EAU.
Conclusions:
- Distinct circulating miRNA profiles are associated with EAU development.
- Upregulation of specific miRNAs, such as miRNA-146a-5p, occurs during EAU.
- Circulating miRNAs may serve as biomarkers and offer insights into the systemic epigenetic changes in uveitis.
