Effect of Brimonidine on the B Cells, T Cells, and Cytokines of the Ocular Surface and Aqueous Humor in Rat Eyes.

PURPOSE: One serious ocular side effect associated with the long-term use of topical brimonidine tartrate is anterior uveitis. This study investigated the changes in the levels of several inflammatory cytokines, B cells, and T cells in rat eyes treated with topical brimonidine tartrate. METHODS: Twenty Sprague-Dawley male rats were divided into 2 groups of 10 rats each. In the brimonidine group, rats were treated with brimonidine 3 times per day for 10 months. The rat cytokine multiplex method was used to determine the levels of cytokines [interleukin (IL)-1α, IL-1ß, IL-2, IL-6, tumor necrosis factor alpha (TNF-α)] in the conjunctiva, cornea, aqueous humor, and lens. The cornea and conjunctiva were subjected to immunohistochemical staining using anti-CD20 antibody and anti-CD3 antibody. RESULTS: The concentrations of IL-1ß, IL-2, and IL-6 in the conjunctiva were significantly lower in the brimonidine group (P = 0.033, 0.017, and 0.016, respectively) than in the control group. Compared to the control group, the concentration of IL-2 in the cornea was also significantly lower in the brimonidine group (P = 0.037). However, in the analysis of the cytokines in the aqueous humor, the concentrations of IL-1ß and IL-2 were significantly higher in the brimonidine group than in the control group (P = 0.016 and 0.008, respectively). There was no significant difference in CD20-positive B-cell and CD3-positive T-cell infiltration of the conjunctival biopsy specimens between the brimonidine group and the control group. Corneal specimens of both groups also showed no infiltration of CD20-positive B cells and CD3-positive T cells. CONCLUSIONS: These results suggest that the increase in some inflammatory cytokines in the aqueous humor after the long-term brimonidine treatment may contribute to the pathogenesis of brimonidine-induced uveitis.