%0 Generic
%A Künzel, Steffen Emil
%C Heidelberg
%D 2022
%F heidok:31721
%R 10.11588/heidok.00031721
%T NCK1/2 are specific mediators of migration in Pericytes and promising targets in ischemic retinopathies
%U https://archiv.ub.uni-heidelberg.de/volltextserver/31721/
%X 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.