Zhang Yao, Zhao Dongwan, Yang Shuai, Yao Haipei, Li Min, Zhao Chun, Zhang Jingfa, Xu Guo-Tong, Li Hui, Wang Fang
Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
Cell Physiol Biochem. 2018;46(4):1704-1715. doi: 10.1159/000489246. Epub 2018 Apr 23.
BACKGROUND/AIMS: Proliferative vitreoretinopathy (PVR) is a severe blinding complication of rhegmatogenous retinal detachment. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is thought to play a pivotal role in the pathogenesis of PVR. Fucoidan, a marine extract, reportedly has many benefits effects in a variety of tissues and organs such as anti-inflammation, anti-oxidative stress, and anti-carcinogenesis. In this study, we investigated the potential role of fucoidan on EMT in RPE cells and its effect on the development of PVR.
MTS, Transwell, and collagen gel contraction assays were employed to measure the viability, migration, and contraction of RPE cells, respectively. mRNA and protein expression were evaluated via real-time quantitative PCR and western blot analysis, respectively. In vivo, a pigmented rabbit model of PVR was established to examine the anti-PVR effect of fucoidan.
Fucoidan reversed the transforming growth factor (TGF)-β1-induced EMT of RPE cells, including the increased expression of α-smooth muscle actin (α-SMA) and fibronectin and down-regulation of E-cadherin in human primary RPE cells. Moreover, the upregulation of phosphorylated Smad2/3 induced by TGF-β1 was suppressed by fucoidan. Fucoidan also inhibited the migration and contraction of RPE cells induced by TGF-β1. In vivo, fucoidan inhibited the progression of experimental PVR in rabbit eyes. Histological findings showed that fucoidan suppressed the formation of α-SMA-positive epiretinal membranes.
Our findings regarding the protective effects of fucoidan on the EMT of RPE cells and experimental PVR suggest the potential clinical application of fucoidan as an anti-PVR agent.
背景/目的：增殖性玻璃体视网膜病变（PVR）是孔源性视网膜脱离的一种严重致盲并发症。视网膜色素上皮（RPE）细胞的上皮-间质转化（EMT）被认为在PVR的发病机制中起关键作用。岩藻依聚糖是一种海洋提取物，据报道在多种组织和器官中具有多种有益作用，如抗炎、抗氧化应激和抗癌作用。在本研究中，我们研究了岩藻依聚糖对RPE细胞EMT的潜在作用及其对PVR发展的影响。
采用MTS、Transwell和胶原凝胶收缩试验分别检测RPE细胞的活力、迁移和收缩能力。分别通过实时定量PCR和蛋白质印迹分析评估mRNA和蛋白质表达。在体内，建立PVR的色素兔模型以研究岩藻依聚糖的抗PVR作用。
岩藻依聚糖逆转了转化生长因子（TGF）-β1诱导的RPE细胞EMT，包括人原代RPE细胞中α-平滑肌肌动蛋白（α-SMA）和纤连蛋白表达增加以及E-钙黏蛋白下调。此外，岩藻依聚糖抑制了TGF-β1诱导的磷酸化Smad2/3上调。岩藻依聚糖还抑制了TGF-β1诱导的RPE细胞迁移和收缩。在体内，岩藻依聚糖抑制了兔眼实验性PVR的进展。组织学结果表明，岩藻依聚糖抑制了α-SMA阳性视网膜前膜的形成。
我们关于岩藻依聚糖对RPE细胞EMT和实验性PVR的保护作用的研究结果表明，岩藻依聚糖作为一种抗PVR药物具有潜在的临床应用价值。
