Thrombospondin-1 Is Produced by Retinal Glial Cells and Inhibits the Growth of Vascular Endothelial Cells
Thrombospondin-1 Is Produced by Retinal Glial Cells and Inhibits the Growth of Vascular Endothelial Cells
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DOI：
10.1159/000362371
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发表时间：
2014-01-01
影响因子：
2.1
通讯作者：
Bringmann, Andreas
中科院分区：
文献类型：
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作者：
Yafai, Yousef;Eichler, Wolfram;Bringmann, Andreas
背景/目的：通过释放抗血管生成因子，Muller胶质细胞在正常和缺血的视网膜中提供血管生成抑制环境。我们确定穆勒细胞是否产生血小板反应蛋白-1（TSP-1），一种已知的血管生成抑制剂。方法：采用ELISA法检测培养的Muller细胞分泌TSP-1的情况。对大鼠视网膜切片和手术切除的人类受试者视网膜膜进行TSP-1和神经胶质标志物波形蛋白的免疫染色。采用DNA合成和迁移实验及Western blotting法检测TSP-1对牛视网膜内皮细胞（BRECs）生长及ERK 1/2激活的影响。结果：培养的苗勒氏细胞在常氧和低氧（0.2%O-2）条件下均可分泌TSP-1。与常氧相比，缺氧时TSP-1的分泌增加。在大鼠视网膜切片中，神经胶质、视网膜神经节和可能的水平细胞被TSP-1染色。非缺氧性视网膜前胶质增生（黄斑皱褶）和增殖性糖尿病视网膜病变患者视网膜前膜中的视网膜胶质细胞分别为TSP-1免疫阳性。外源性TSP-1可抑制VEGF诱导的BRECs增殖和迁移，降低BRECs中ERK 1/2的磷酸化水平。结论：Muller细胞是正常和缺血视网膜中oTSP-1的主要来源之一。胶质细胞来源的TSP 1可以抑制缺血视网膜中的血管生成反应。(C)2014 S. Karger AG，巴塞尔
Background/Aims: By the release of antiangiogenic factors, Muller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Muller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. Methods: Secretion of TSP-1 by cultured Muller cells was determidewith ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively. Results: Cultured Muller clsecrete TSP-1 under normoxic and hypoxic (0.2% O-2) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF-induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs. Conclusion: The data suggest that Muller cells are one major source oTSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina. (C) 2014 S. Karger AG, Basel