Developmental regression of hyaloid vasculature is triggered by neurons.
Developmental regression of hyaloid vasculature is triggered by neurons.
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DOI：
10.1084/jem.20151966
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发表时间：
2016-06-27
期刊：
影响因子：
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通讯作者：
Kubota Y
中科院分区：
文献类型：
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作者：
Yoshikawa Y;Yamada T;Tai-Nagara I;Okabe K;Kitagawa Y;Ema M;Kubota Y
Kubota和他的同事们发现，在眼睛发育过程中，神经元隔离VEGF以修剪血管。 血管的发育不仅涉及血管的生长，还涉及短暂的或不必要的血管的消退。玻璃体血管系统是胎儿眼中的临时循环系统，当视网膜血管开始生长时，玻璃体血管系统自发地退化。玻璃体血管不能退化导致人类疾病，持续性增生性原始玻璃体，其引起严重的眼内出血并损害视觉功能。然而，介导玻璃体血管自发消退的内源性程序的机制还不清楚。在这项研究中，我们确定了一个强大的开关触发这个程序的神经元在小鼠中。血管内皮生长因子（VEGF）受体2（VEGFR2）的显著上调发生在视网膜神经元出生后通过远端多能中胚层增强子，血管内皮细胞特异性增强VEGFR2。神经元VEGFR2的基因缺失中断了这一程序，导致即使在出生后的后期也持续存在大量玻璃体血管。这种异常是由玻璃体腔中过量的VEGF蛋白引起的，这是VEGF神经元隔离受损的结果。总的来说，我们的数据表明，神经元触发过渡从胎儿到出生后的视网膜循环系统。
Kubota and colleagues show that neurons sequester VEGF to prune blood vessels during eye development. Vascular development involves not only vascular growth, but also regression of transient or unnecessary vessels. Hyaloid vasculature is the temporary circulatory system in fetal eyes, which spontaneously degenerates when the retinal blood vessels start to grow. Failure of the hyaloid vessels to regress leads to disease in humans, persistent hyperplastic primary vitreous, which causes severe intraocular hemorrhage and impairs visual function. However, the mechanism underlying the endogenous program that mediates spontaneous regression of the hyaloid vessels is not well understood. In this study, we identify a robust switch triggering this program directed by neurons in mice. Marked up-regulation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) occurs in retinal neurons just after birth via distal-multipotent-mesodermal enhancer, a hemangioblast-specific enhancer of VEGFR2. Genetic deletion of neuronal VEGFR2 interrupts this program, resulting in massive hyaloid vessels that persist even during late postnatal days. This abnormality is caused by excessive VEGF proteins in the vitreous cavity as a result of impairment in the neuronal sequestration of VEGF. Collectively, our data indicate that neurons trigger transition from the fetal to the postnatal circulatory systems in the retina.