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Abstract

The particular focus of my dissertation is on pericytes which are mural cells that surround capillaries and control angiogenesis and capillary barrier function. I investigate endothelial cell-derived platelet-derived growth factor-B (PDGF-B) signaling during sprouting angiogenesis in health and disease. With this, I show that “activated” α-SMA-expressing pericytes cover angiogenic sprouts and pathological neovascular tufts (NVTs) in a mouse model of oxygen-induced retinopathy. By genetic lineage tracing experiments, this work demonstrates that pericytes acquire α-SMA expression during pathological NVT formation. Pericyte depletion through inducible endothelial-specific knockout of the ligand Pdgf-b decreases this NVT formation, but also impairs revascularization. Moreover, I demonstrate that loss of Nck1 and Nck2 in mural cells prevents NVT formation and vascular leakage and promotes revascularization, suggesting NCK signaling as a potential target for the treatment of retinopathies.