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.
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