Experimental models of retinal angiogenesis: the effect of angiopoietin-2 and TNFα modulation

Proligerative retinopathies, such as proliferative diabetic retinoplathy and retinopathy of prematurity are common causes of blindness. Epidemiologic studies prpose an increase in diabetic patients over the coming years and thus the amount of people afrfected by proliferative retinopathy will also increase. Vascular endothelial growth factor (VEGF) has been identiefied as a key mo9lecular target in this desease and anti-VEGF drugs have found their way into the clinic, yet. The experiments presented in this thesis were performed to further investigate the molecular mechanisms of physiological and pathological retinal angiogenisis and to increase understanding of the pathogenenis of pathological neovascularization. Based on studies demonstrating the importance of the angiopoietin-2 (Ang2)/VEGF balance in angiogenesis, one part of the studies was focused on the effects of Ang2 overexpression and deficiency in experimental nouse models of retinal angiogenesis. In the next part, we aimed at establishing a method to analyse spatial inflammatory- and angiogenesis assocated gene expression and their localized regulation by hypoxia in the retina. Furthermore, we investigated the contribution of inflammatory factors, i.e. tumor necrosis factor α (TNFα) in the process of retinal neovascularization. Finally, we tested the influence of intravitreally administered thalidomide, which is a drug that inhibits TNFα signalling and interferes with VEGF signalling, on preretinal neovascularization