Programm                 "Degeneration und Regeneration– Grundlagen, Diagnostik und Therapie"


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Abstract
Abstract

Control Mechanisms of Retinal Neovascularization

Eichler W. 
University Eye Hospital, Leipzig

Retinal neovascularization is a common complication in patients with advanced diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Blood vessel growth is characterized by actively migrating and proliferating endothelial cells and is associated with a shift in the balance of (i) pro-angiogenic mediators and (ii) endogenous angiogenesis inhibitors. Production of vascular endothelial growth factor (VEGF), a potent enhancer of angiogenesis and vascular permeability, is controlled by local oxygen concentrations; i.e., hypoxia results in increasing VEGF levels. Pigment epithelium-derived factor (PEDF) seems to counter the angiogenic effects of VEGF; PEDF levels remain high when oxygen concentration is normal but become decreased in hypoxic conditions. The VEGF/PEDF ratio determines whether neovascularization is inhibited (in healthy retinal tissue) or an abnormal blood vessel growth is stimulated (in hypoxic / ischemic conditions).
Retinal glial (Müller) cells express and release VEGF as well as PEDF, and decreasing oxygen concentrations result in enhanced VEGF / PEDF ratios. A novel mechanism of ocular angiogenic homeostasis was uncovered by in-vitro experiments showing that Müller-cell derived PEDF is suppressed by VEGF in a dose-dependent manner. The findings suggest also that Müller cells can generate a permissive condition for angiogenesis in the ischemic retina although the onset of retinal endothelial cell proliferation requires another triggering signal w


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