Abstract
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.
Highlights
Rats injected with Melaninassociated antigen (MAA) began to develop clinical signs of experimental autoimmune anterior uveitis (EAAU) at 10 dpi
Rats injected with low-dose miR-146a had significantly lower clinical activity scores at 15 and 17 dpi than rats injected with MAA (p < 0 01 and p = 0 02, resp.; n = 10)
High-dose miR-146a treatment was associated with lower clinical activity scores at 15, 17, and 20 dpi compared with treatment with MAA (p < 0 01 for all paired comparisons; n = 10)
Summary
43% to 70% of these cases are anterior uveitis [1, 2, 3]. This strategy is cumbersome in that recurrent disease attacks and prolonged steroid use often lead to ocular complications and deterioration of vision [4, 5]. Systemic immunomodulatory agents with steroid-sparing effects are needed in selected cases. Hepatic, renal, or bone marrow adverse events are not uncommon [6, 7]. New methods of local treatment with steroid-sparing effects are highly desired
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