Molecular Signals Involved in Ocular Neovascularization

描述(摘自申请人的摘要)：本提案的计划是 研究眼部相关因素之间的相互作用 低氧诱导的新生血管-血管内皮生长因子 低氧诱导因子-1、血管生成素-2和胰岛素样生长因子 (IGF-1)。该计划是同时使用转基因和基因转移方法来 检验以下假设：1)血管内皮生长因子在体内的表达增加 视网膜将导致深毛细血管床的视网膜新生血管 但不是像缺血性视网膜病变那样的浅表毛细血管。2) HIF-1α表达增加将更接近于模拟缺血性视网膜病变 因为它上调了除血管内皮生长因子外的其他因子。3)增加 在视网膜内产生的IGF-1将不足以产生 视网膜新生血管，但会增强血管内皮生长因子的作用。4)增加 视网膜色素上皮细胞(RPE)中VEGF的表达足以 导致脉络膜新生血管。5)血管紧张素转换酶2表达增强。 视网膜导致新生血管的消退，而Ang2和 血管内皮生长因子促进新生血管形成。

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.