透明的角膜是視覺所必需的,，這也是為什么眼睛進化成無血管滋養(yǎng)角膜原因,。但是，對于世界上數(shù)百萬人來說,，眼疾或創(chuàng)傷能引起血管生長,，引起失明。
一項新的西北醫(yī)學研究已鑒定出一個在維持人與老鼠角膜透明度起這要作用的基因--可能被用作基因治療來治療導致失明的疾病,。文章發(fā)表在《國家科學研究院學報》（PNAS,Proceedings of the National Academy of Sciences）上,。
"我們相信,，我們已發(fā)現(xiàn)了眼睛內(nèi)阻止血管形成,、保護角膜透明度的主要調(diào)節(jié)基因，"文章作者Tsutomu Kume這樣說,，他是西北大學費因伯格醫(yī)學院的醫(yī)學副教授,，也是費因伯格心血管研究所的研究人員。
基因FoxC1的存在是早就已知的,，但是它在維持角膜澄清的作用是一新發(fā)現(xiàn),。用這個基因缺失的特殊品種小鼠進行研究，Kume與同事們發(fā)現(xiàn)可條紋化角膜和遮擋光線的異常血管形態(tài)或異常血管,。
當Kume發(fā)現(xiàn)突變體小鼠的角膜血管量,，他告知合作者--加拿大艾伯塔大學眼科學與醫(yī)學遺傳學教授Ordan Lehmann醫(yī)學博士。
Lehmann發(fā)現(xiàn)他的病人眼睛里也有異常血管生長,，這些病人有單拷貝的FoxC1基因突變體,，患先天性青光眼。
"令人興奮的事是FoxC1的喪失導致了角膜的血管化作用,，這意味著增加這個基因的水平可能有助于阻止可能在多種眼疾中導致失明的血管異常生長,，" 文章另一作者Lehmann說。"那就是希望,。"一個可能的用途就是用于角膜移植,，而角膜移植的主要問題就是移植角膜上的新血管生長,。
Kume接下來計劃在小鼠上測試基因治療，觀察注射FoxC1是否抑制角膜中血管的形成,。（生物谷bioon.com）
doi:doi:10.1073/pnas.1109540109
PMC:
PMID:
Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vasculargrowth.
Seo S, Singh HP, Lacal PM, Sasman A, Fatima A, Liu T, Schultz KM, Losordo DW, Lehmann OJ, Kume T.
Abstract Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld-Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1(-/-)) or neural crest (NC)-specific (NC-Foxc1(-/-)) null mutation display excessive growth of corneal blood and lymphatic vessels. This is associated with disorganization of the extracellular matrix and increased expression of multiple matrix metalloproteinases. Heterozygous mutants (Foxc1(+/-) and NC-Foxc1(+/-)) exhibit milder phenotypes, such as disrupted limbal vasculature. Moreover, environmental exposure to corneal injury significantly increases growth of both blood and lymphatic vessels in both Foxc1(+/-) and NC-Foxc1(+/-) mice compared with controls. Notably, this amplification of the angiogenic response is abolished by inhibition of VEGF receptor 2. Collectively, these findings identify a role for FoxC1 in inhibiting cornealangiogenesis, thereby maintaining corneal transparency by regulating VEGF signaling.
