The role of renin-angiotensin and growth factors in developmental and pathological neovascularization in the retina

在新生婴儿的正常视网膜中，内层的血管尚未完全形成。视网膜氧的减少可能刺激这些血管生长，从而启动视网膜细胞中生长剂的产生。一旦新血管形成，视网膜的含氧量就会恢复正常，生长剂和血管的生长都会减少。视网膜中氧含量的长期降低会对视力造成严重后果。事实上，在一些眼病中，新血管生长过度，血管没有正确形成，导致出血，最终失明。当放置在高氧恒温箱后，早产儿的氧气环境减少时，就会发生这种事件。此外，在长期糖尿病患者中，视网膜的含氧量会随着视网膜血管受损而下降。要了解视网膜发育和疾病中导致新血管生长的事件，需要确定生长因子及其在视网膜中的位置。最近，人们发现生长因子肾素-血管紧张素是在视网膜中产生的，糖尿病患者对其的阻断减缓了新视网膜血管生长的进展。肾素-血管紧张素可能通过增加其他视网膜生长因子的产生而引起其生长效应。本提案将研究肾素-血管紧张素和其他生长因子在新生大鼠视网膜发育和眼病中的作用。这一信息可能会导致对新生婴儿视网膜血管形成的进一步了解，并产生以视网膜血管生长为特征的眼病的新治疗方法。

In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some eye diseases new blood vessel growth is excessive and the vessels are not properly formed, which leads to hemorrhage and ultimately blindness. Such events occur when the oxygen environment of premature babies is reduced after placement in high oxygen incubators. Also, in long-term diabetes, the oxygen levels of the retina falls as the retinal vessels become damaged. To understand the events that cause new vessel growth in retinal development and disease requires identification of the growth agents and their location in the retina. Very recently it has been found that the growth agent renin-angiotensin is made in the retina, and that its blockade in diabetic patients slows the progression of new retinal vessel growth. Renin-angiotensin is likely to cause its growth effects by increasing the production of other retinal growth agents. This proposal will study the role of renin-angiotensin and other growth agents in the developing newborn rat retina and in eye diseases. This information may lead to a further understanding of how blood vessels form in the retinas of newborn babies, and the production of new treatments for eye diseases characterized by blood vessel growth in the retina.