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  μ g) or high-dose (1.5  μ g) 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- κ B) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF- κ B 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-) 1 β , IL-6, and IL-12 and interferon- (IFN-) γ and upregulation of IL-10 and IL-17 were noted. The decreased NF- κ B 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- κ B. miR-146a might be a new treatment choice for uveitis.