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Updated: Mar 30, 2026
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
MicroRNAs in retina during development of experimental autoimmune uveoretinitis in rats
Takayo Watanabe1, Hiroshi Keino1, Akihiko Kudo2
1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
Purpose:
To determine the changes in the expression profiles of microRNAs (miRNAs) in retinas during the development of experimental autoimmune uveoretinitis (EAU) in rats.
Methods:
The levels of interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were measured in aqueous humour samples and supernatants of homogenised posterior eye cups obtained from Lewis rats immunised with interphotoreceptor retinoid binding protein peptide (R14) and complete Freund's adjuvant. Microarray analysis was performed to determine the miRNA profiles in the retina of eyes with EAU on days 0 (baseline), 7, 14 and 21 after immunisation.
Results:
The levels of IL-1β and MCP-1 in the aqueous humour and the supernatants of posterior eye cups were significantly elevated in eyes with EAU, and the levels corresponded with the stage of the EAU. On day 14 after immunisation, the expressions of nine miRNAs (miRNA-223, 142-5p, 142-3p, 21, 146a, 146b, 1949, 1188-3p and 193) were significantly elevated, and the expressions of four miRNAs (miRNA-181a, 183*, 124* and 331) were downregulated relative to the baseline. Quantitative PCR analyses confirmed the elevation of miRNA-223 and miRNA-146 and the downregulation of miRNA-181a in retinas with EAU on day 14 after immunisation. In situ hybridisation confirmed increased expression of miR-223 and miR-146 in retinas with EAU.
Conclusions:
Several miRNAs were significantly increased or decreased in retinas during the course of EAU. The expression of miR-223 and miR-146a corresponded with the clinical score of the EAU and elevation of IL-1β/MCP-1 in the eye with EAU. Further studies are required to clarify the role of miRNA in eyes with autoimmune uveoretinitis.
Insights
This study identified specific microRNAs (miRNAs) that change during experimental autoimmune uveoretinitis (EAU) development in rats. Upregulated miR-223 and miR-146a levels correlated with disease severity and inflammation markers.
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 and play roles in inflammation and immunity.
Purpose of the Study:
- To investigate changes in retinal microRNA expression profiles during the development of EAU in rats.
- To correlate miRNA expression with inflammatory markers and disease progression.
Main Methods:
- Lewis rats were immunized to induce EAU.
- Interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) levels were measured in ocular fluids.
- Microarray analysis was used to profile retinal miRNA expression at different stages of EAU.
- Quantitative PCR and in situ hybridization validated key miRNA changes.
Main Results:
- IL-1β and MCP-1 levels were significantly elevated in EAU eyes, correlating with disease stage.
- Nine miRNAs, including miR-223 and miR-146a, were upregulated on day 14 post-immunization.
- Four miRNAs, including miR-181a, were downregulated.
- Increased expression of miR-223 and miR-146 was confirmed in EAU retinas.
Conclusions:
- Several miRNAs are differentially expressed in the retina during EAU.
- miR-223 and miR-146a expression levels correlate with EAU clinical scores and ocular inflammation.
- Further research is needed to elucidate the specific roles of these miRNAs in autoimmune uveoretinitis.
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