MicroRNA-146a Alleviates Experimental Autoimmune Anterior Uveitis in the Eyes of Lewis Rats

Purpose. This study aimed to determine the effect and roles of microRNA (miRNA, miR) treatment in experimental autoimmune anterior uveitis (EAAU). Materials and Methods. Uveitis was induced in Lewis rats by simultaneous injections of bovine melanin-associated antigen into the hind footpad and the intraperitoneal cavity. The animals were injected intravitreally with low-dose (0.5 μg) or high-dose (1.5 μg) miR-146a. The clinical scores, leukocyte count in the aqueous humor, and histology were assessed. Cytokine changes were evaluated by relative mRNA expression and enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF-κB was performed by electrophoretic mobility shift assay (EMSA). Results. Treatment with miR-146a significantly attenuated clinical scores and leukocyte infiltration in a dose-dependent manner, a result that was compatible with histological findings. Following miR-146a injections, downregulation of interleukin- (IL-) 1β, IL-6, and IL-12 and interferon- (IFN-) γ and upregulation of IL-10 and IL-17 were noted. The decreased NF-κB expression on immunofluorescence and Western blotting and reduced DNA-binding activity on EMSA were demonstrated following miR-146a treatment. Conclusions. miR-146a effectively reduced intraocular inflammation in EAAU through the inhibition of NF-κB. miR-146a might be a new treatment choice for uveitis.

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