VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR EXPRESSION IN A MOUSE MODEL OF RETINAL NEOVASCULARIZATION
VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR EXPRESSION IN A MOUSE MODEL OF RETINAL NEOVASCULARIZATION
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DOI：
10.1073/pnas.92.3.905
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发表时间：
1995-01-31
影响因子：
11.1
通讯作者：
SMITH, LEH
中科院分区：
文献类型：
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作者：
PIERCE, EA;AVERY, RL;SMITH, LEH
视网膜的新生血管性疾病是全世界失明的主要原因。在许多视网膜疾病中，缺氧被认为是新生血管形成的常见前兆，但参与缺氧新生血管反应的因素尚未完全确定。为探讨血管内皮生长因子/血管通透性因子（VEGF/VPF）在视网膜新生血管形成中的作用，本研究观察了增殖性视网膜病变小鼠模型中VEGF/VPF mRNA和蛋白的表达。RNA（北方）印迹分析显示，视网膜VEGF/VPF mRNA的表达增加3倍之间6和12小时的相对视网膜缺氧，并保持在新血管形成的发展过程中升高。原位杂交显示VEGF/VPF mRNA定位于视网膜内核层的胞体。免疫组织化学共聚焦显微镜显示，VEGF/VPF蛋白水平增加的时间过程类似的mRNA。视网膜内核层中产生VEGF/VPF的细胞在形态学上被鉴定为Muller细胞。这些数据表明，VEGF/WF在视网膜中的表达在视网膜缺血诱导的眼新生血管的发展中起着核心作用。
Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Muller cells. These data suggest that VEGF/WF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization.