Molecular Signals Involved in Ocular Neovascularization

描述（来自申请人的摘要）：本提案的计划是 研究与眼部疾病有关的因素之间的相互作用， 新生血管形成-血管内皮生长因子（VEGF），缺氧诱导 因子-1（HIF-1）、血管生成素2（Ang 2）和胰岛素样生长因子 （IGF-1）。该计划是使用转基因和基因转移的方法， 检验以下假设：1）VEGF在内皮细胞中的表达增加， 视网膜将导致来自深毛细血管床的视网膜新生血管形成 而不是缺血性视网膜病中出现的浅表毛细血管。（二） HIF-1 α表达增加将更接近缺血性视网膜病变 因为它会上调除VEGF外的其他因子。3)增加 在视网膜内层产生IGF-1将不足以产生 视网膜新生血管，但会增强VEGF的作用。4)增加 VEGF在视网膜色素上皮细胞（RPE）中的表达足以 引起脉络膜新生血管。5)血管生成素2表达增加， 视网膜引起新生血管的消退，而Ang 2和 VEGF促进新血管形成。

DESCRIPTION (From the Applicant's Abstract): The plan of this proposal is to study interactions between factors that have been implicated in ocular neovascularization-vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF-1), angiopoietin 2 (Ang2), and insulin-like growth factor (IGF-1). The plan is to use both transgenic and gene transfer approaches to test the following hypotheses: 1) Increased expression of VEGF in the inner retina will result in retinal neovascularization from the deep capillary bed but not the superficial capillaries as occurs in ischemic retinopathies. 2) Increased expression of HIF-1alpha will more closely mimic ishemic retinopathy because it upregulates other factors in addition to VEGF. 3) Increased production of IGF-1 in the inner retina will not be sufficient to produce retinal neovascularization, but will enhance the effects of VEGF. 4) Increased expression of VEGF in retinal pigment epithelial cells (RPE) is sufficient to cause choroidal neovascularization. 5) Increased expression of Ang2 in the retina causes regression of neovascularization, while coexpression of Ang2 and VEGF promotes neovascularization.