研究人员报道说角膜通过表达一种可溶性受体来保持清洁,这种受体能够困住能够阻碍视觉的血管生长的因子。乔治亚医学院和肯塔基州大学的研究人员进行的这项研究的结果公布再10月26日的《自然》杂志上。
研究人员发现,当血管内皮生长因子A的一种受体sflt-1被清除掉时,能阻碍视觉的血管就开始生长。
这篇文章的第一作者Balamurali K. Ambati形象地将Sflt-1比作“手铐”。研究人员使用从中和抗体到基因敲除的多种方法来打开这个“手铐”,但小鼠的角膜仍然形成血管。
正常的角膜上是不应该布满血管的,因为它有大量的抗血管形成分子。但是,研究人员发现敲除Sflt-1以外的分子不会导致血管进入角膜。
已经知道,sflt-1的功能是VEGF受体,它大量存在于血管壁细胞膜上,帮助启动血管的生长。事实上,对它的可溶性形式的研究主要集中再抗肿瘤潜力上。
它再角膜清理中的这种新发现的功能为人们利用它来清除角膜中异常生长的血管开启了大门。
在两种角膜中长了血管的小鼠模型——corn1和Pax6小鼠中,研究人员发现角膜没有表达sflt-1蛋白。当给予重组的sflt-1时,小鼠的角膜变得清洁。Pax6小鼠具有一种突变形式的Pax6蛋白,这种蛋白与眼睛的发育有关。
英文原文:
Corneal avascularity is due to soluble VEGF receptor-1
Corneal avascularity—the absence of blood vessels in the cornea—is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.