VEGF-TRAPR1R2 suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier
VEGF-TRAPR1R2 suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier
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DOI：
10.1002/jcp.10246
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发表时间：
2003-05-01
影响因子：
5.6
通讯作者：
Campochiaro, PA
中科院分区：
文献类型：
--
作者：
Saishin, Y;Saishin, Y;Campochiaro, PA
血管内皮生长因子(VEGF)在视网膜新生血管和糖尿病黄斑水肿的发生发展中起核心作用。也有证据表明，血管内皮生长因子是脉络膜新生血管的重要刺激因子。在这项研究中，我们研究了一种特定的血管内皮生长因子抑制剂，血管内皮生长因子陷阱(R1R2)，在这些疾病过程的模型中的作用。血管内皮生长因子TRAP(R1R2)是一种融合蛋白，它将从血管内皮生长因子受体1和2的胞外区提取的配体结合元件融合到IgG1的Fc部分。皮下注射或单次玻璃体内注射血管内皮生长因子陷阱(R1R2)强烈抑制激光诱导Bruch膜破裂小鼠的脉络膜新生血管。皮下注射血管内皮生长因子陷阱(R1R2)也显著抑制了在光感受器中表达血管内皮生长因子的转基因小鼠的视网膜下新生血管。在两种血管内皮生长因子诱导血-视网膜屏障(BRB)破裂的模型中，一种是将重组的VEGF注射到玻璃体腔内，另一种是在转基因小鼠的视网膜中诱导VEGF的表达，VEGF-TRAP(R1R2)显著减少了血-视网膜屏障的破裂。这些数据证实了血管内皮生长因子是脉络膜新生血管形成的关键刺激因子，提示血管内皮生长因子陷阱(R1R2)可能为治疗脉络膜新生血管和糖尿病黄斑水肿患者提供一种新的药物。J.细胞。物理。195：241-248,2003。(C)2003年Wiley-Liss，Inc.
Vascular endothelial growth factor (VEGF) plays a central role in the development of retinal neovascularization and diabetic macular edema. There is also evidence suggesting that VEGF is an important stimulator for choroidal neovascularization. In this study, we investigated the effect of a specific inhibitor of VEGF, VEGF-TRAP(R1R2), in models for these disease processes. VEGF-TRAP(R1R2) is a fusion protein, which combines ligand binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG1. Subcutaneous injections or a single intravitreous injection of VEGF-TRAP(R1R2) strongly suppressed choroidal neovascularization in mice with laser-induced rupture of Bruch's membrane. Subcutaneous injection of VEGF-TRAP(R1R2) also significantly inhibited subretinal neovascularization in transgenic mice that express VEGF in photoreceptors. in two models of VEGF-induced breakdown of the blood-retinal barrier (BRB), one in which recombinant VEGF is injected into the vitreous cavity and one in which VEGF expression is induced in the retina in transgenic mice, VEGF-TRAP(R1R2) significantly reduced breakdown of the BRB. These data confirm that VEGF is a critical stimulus for the development of choroidal neovascularization and indicate that VEGF-TRAP(R1R2) may provide a new agent for consideration for treatment of patients with choroidal neovascularization and diabetic macular edema. J. Cell. Physiol. 195: 241 -248, 2003. (C) 2003 Wiley-Liss, Inc.