研究人員報道說角膜通過表達一種可溶性受體來保持清潔，這種受體能夠困住能夠阻礙視覺的血管生長的因子,。喬治亞醫(yī)學(xué)院和肯塔基州大學(xué)的研究人員進行的這項研究的結(jié)果公布再10月26日的《自然》雜志上,。
研究人員發(fā)現(xiàn)，當血管內(nèi)皮生長因子A的一種受體sflt-1被清除掉時,，能阻礙視覺的血管就開始生長,。
這篇文章的第一作者Balamurali K. Ambati形象地將Sflt-1比作“手銬”。研究人員使用從中和抗體到基因敲除的多種方法來打開這個“手銬”,，但小鼠的角膜仍然形成血管,。
正常的角膜上是不應(yīng)該布滿血管的，因為它有大量的抗血管形成分子。但是,，研究人員發(fā)現(xiàn)敲除Sflt-1以外的分子不會導(dǎo)致血管進入角膜,。
已經(jīng)知道，sflt-1的功能是VEGF受體,，它大量存在于血管壁細胞膜上,，幫助啟動血管的生長。事實上,，對它的可溶性形式的研究主要集中再抗腫瘤潛力上,。
它再角膜清理中的這種新發(fā)現(xiàn)的功能為人們利用它來清除角膜中異常生長的血管開啟了大門。
在兩種角膜中長了血管的小鼠模型——corn1和Pax6小鼠中,，研究人員發(fā)現(xiàn)角膜沒有表達sflt-1蛋白,。當給予重組的sflt-1時，小鼠的角膜變得清潔,。Pax6小鼠具有一種突變形式的Pax6蛋白,，這種蛋白與眼睛的發(fā)育有關(guān)。
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.
