Matrix metalloproteinase and cytokine expression in Tenon fibroblasts during scar formation after glaucoma filtration or implant surgery in rats
Matrix metalloproteinase and cytokine expression in Tenon fibroblasts during scar formation after glaucoma filtration or implant surgery in rats
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DOI：
10.1002/cbf.2923
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发表时间：
2013-08-01
影响因子：
3.6
通讯作者：
Kiuchi, Yoshiaki
中科院分区：
文献类型：
--
作者：
Nakamura-Shibasaki, Momoko;Ko, Ji-Ae;Kiuchi, Yoshiaki
青光眼手术的失败通常是由于术后瘢痕形成（纤维化），成纤维细胞在其中发挥重要作用的过程。我们通过检测青光眼手术后从大鼠分离的Tenon成纤维细胞中基质金属蛋白酶和细胞因子的表达来研究这种瘢痕形成的分子机制。在一只眼睛中进行滤过手术，在另一只眼睛中进行植入手术;手术后从滤过泡周围的组织中分离Tenon成纤维细胞。培养细胞，通过逆转录-聚合酶链反应、免疫印迹和明胶酶谱分析检测基质金属蛋白酶（MMPs）的表达。还用多重阵列测定培养物上清液的细胞因子。MMP-1和MMP-3 mRNA和蛋白质的量在植入手术后分离的细胞中比在滤过手术后分离的细胞中更大，在前一次手术后瘢痕形成的进展更完全。滤过手术后分离的细胞分泌的白细胞介素-6（IL-6）大于植入手术后分离的细胞。在滤过手术后分离的细胞中通过RNA干扰去除IL-6增加了这些细胞中MMP-1和MMP-3的表达。因此，这些结果表明，MMP-1和MMP-3在Tenon成纤维细胞的表达调节IL-6期间，并可能发挥重要作用，青光眼手术后的瘢痕形成。版权所有（c）2012约翰威利父子有限公司
Failure of surgery for glaucoma is usually due to post-surgical scarring (fibrosis), a process in which fibroblasts play a prominent role. We investigated the molecular mechanisms of such scarring by examining the expression of matrix metalloproteinases and cytokines in Tenon fibroblasts isolated from rats after glaucoma surgery. Filtration surgery was performed in one eye and implant surgery in the other; and Tenon fibroblasts were isolated from the tissue surrounding the bleb after surgery. The cells were cultured and examined for the expression of matrix metalloproteinases (MMPs) by reverse transcription-polymerase chain reaction, immunoblot and gelatin zymographic analyses. Culture supernatants were also assayed for cytokines with a multiplex array. The amounts of MMP-1 and MMP-3 mRNAs and proteins were greater in cells isolated after implant surgery than in those isolated after filtration surgery, with the progression of scar formation being more complete after the former surgery. The secretion of interleukin-6 (IL-6) by cells isolated after filtration surgery was greater than that for cells isolated after implant surgery. Depletion of IL-6 by RNA interference in cells isolated after filtration surgery increased the expression of MMP-1 and MMP-3 in these cells. These results thus suggest that the expression of MMP-1 and MMP-3 in Tenon fibroblasts is regulated by IL-6 during, and may play an important role in, scar formation after glaucoma surgery. Copyright (c) 2012 John Wiley & Sons, Ltd.