Nagasaka Yosuke, Kaneko Hiroki, Ye Fuxiang, Kachi Shu, Asami Tetsu, Kato Seiichi, Takayama Kei, Hwang Shiang-Jyi, Kataoka Keiko, Shimizu Hideyuki, Iwase Takeshi, Funahashi Yasuhito, Higuchi Akiko, Senga Takeshi, Terasaki Hiroko
Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):221-229. doi: 10.1167/iovs.16-20513.
Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR.
Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells.
Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (αSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities.
These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.
增殖性玻璃体视网膜病变（PVR）是最严重的眼部疾病之一。视网膜细胞的纤维化改变被认为与PVR的发病机制有关。视网膜色素上皮（RPE）细胞的上皮-间质转化（EMT）是PVR中纤维血管膜（FVM）发病机制的主要概念之一。在本研究中，我们检测了PVR患者人FVM中小窝蛋白-1（Caveolin-1）的表达。我们还研究了Caveolin-1在PVR发病机制中的作用。
对人FVM和患有PVR的小鼠眼睛进行蛋白质免疫印迹法、实时聚合酶链反应和免疫组织化学检测。使用原代人及小鼠RPE细胞进行细胞迁移试验，以评估Caveolin-1在EMT中的作用。
Caveolin-1在人FVM中表达，并在患有PVR的小鼠眼睛中上调。在敲除或敲低Caveolin-1的RPE细胞中，α平滑肌肌动蛋白（αSMA）表达和迁移能力增加，而紧密连接蛋白-1（ZO-1）免疫组织化学显示ZO-1的形态和表达降低。此外，迁移试验表明，Caveolin-1减少会增加RPE细胞的迁移能力。
这些结果表明，RPE细胞中的Caveolin-1通过阻断EMT来预防PVR。
