Temporal requirement of RPE-derived VEGF in the development of choroidal vasculature.
Temporal requirement of RPE-derived VEGF in the development of choroidal vasculature.
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DOI：
10.1111/j.1471-4159.2010.06573.x
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发表时间：
2010-03
影响因子：
4.7
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Le YZ;Bai Y;Zhu M;Zheng L
血管内皮生长因子(VEGF-A或VEGF)是视网膜和脉络膜血管发育的重要生长因子。为了确定视网膜色素上皮(RPE)来源的血管内皮生长因子在脉络膜血管发育中的时间需求，我们使用可诱导的Cre/LOX系统产生了条件性血管内皮生长因子基因敲除小鼠。免疫印迹和免疫组织化学方法证实RPE来源的血管内皮生长因子缺失。视网膜功能和结构分别采用视网膜电图仪和组织学方法进行评价。用荧光标记的脉络膜平板，用计算机辅助半定量分析脉络膜血管密度。在胚胎第10天(E10)或胚胎第13天(E13)诱导RPE特异性的血管内皮生长因子破坏两天可导致脉络膜血管密度、光感受器功能和光感受器外核层厚度的可调节下降。E15后RPE产生的血管内皮生长因子的丢失不会在脉络膜血管以及光感受器功能和形态上造成可检测到的缺陷。这些结果表明，RPE来源的血管内皮生长因子在胚胎第15天前器官发生的脉络膜血管发育中起关键作用。
Vascular endothelial growth factor (VEGF-A or VEGF) is a potent growth factor for the development of retinal and choroidal vasculatures. To define the temporal requirement of the retinal pigmented epithelium (RPE)-derived VEGF in choroidal vascular development, we generated conditional VEGF knockout mice using an inducible Cre/lox system. The loss of the RPE-derived VEGF was confirmed with immunoblotting and immunohistochemistry. Retinal function and structure were assessed with electroretinography and histology, respectively. Choroidal vascular density was analyzed with computer-assisted semi-quantitative assay using fluorescently labeled choroidal flat-mounts. Induction of RPE-specific VEGF disruption at embryonic day 10 (E10) or E13 for two days caused regulatable decreases in choroidal vascular density, photoreceptor function, and photoreceptor outer nuclear layer thickness. The loss of the RPE-produced VEGF after E15 did not cause detectable defects in choroidal vasculatures and photoreceptor function and morphology. These results suggest that the RPE-derived VEGF plays a critical role in choroidal vascular development during organogenesis before embryonic day 15.
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