Shin Hye-Young, Lee Hyun-Seung, Lee Young Chun, Kim Su-Young
1 Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea , Seoul, Korea.
2 Department of Pediatrics, College of Medicine, The Catholic University of Korea , Seoul, Korea.
J Ocul Pharmacol Ther. 2015 Dec;31(10):623-6. doi: 10.1089/jop.2015.0067. Epub 2015 Sep 24.
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.
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-1β, 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.
The concentrations of IL-1β, 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-1β 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.
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.
长期使用局部用酒石酸溴莫尼定的一种严重眼部副作用是前葡萄膜炎。本研究调查了局部用酒石酸溴莫尼定治疗的大鼠眼睛中几种炎性细胞因子、B细胞和T细胞水平的变化。
将20只Sprague-Dawley雄性大鼠分为2组，每组10只。在溴莫尼定组中，大鼠每天接受3次溴莫尼定治疗，持续10个月。采用大鼠细胞因子多重检测法测定结膜、角膜、房水和晶状体中细胞因子[白细胞介素（IL）-1α、IL-1β、IL-2、IL-6、肿瘤坏死因子α（TNF-α）]的水平。角膜和结膜用抗CD20抗体和抗CD3抗体进行免疫组织化学染色。
溴莫尼定组结膜中IL-1β、IL-2和IL-6的浓度显著低于对照组（分别为P = 0.033、0.017和0.016）。与对照组相比，溴莫尼定组角膜中IL-2的浓度也显著降低（P = 0.037）。然而，在房水细胞因子分析中，溴莫尼定组IL-1β和IL-2的浓度显著高于对照组（分别为P = 0.016和0.008）。溴莫尼定组与对照组结膜活检标本中CD20阳性B细胞和CD3阳性T细胞浸润无显著差异。两组角膜标本也未显示CD20阳性B细胞和CD3阳性T细胞浸润。
这些结果表明，长期溴莫尼定治疗后房水中某些炎性细胞因子的增加可能有助于溴莫尼定诱导的葡萄膜炎的发病机制。
