title: NCK1/2 are specific mediators of migration in Pericytes and promising targets in ischemic retinopathies creator: Künzel, Steffen Emil subject: ddc-610 subject: 610 Medical sciences Medicine description: 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. date: 2022 type: Dissertation type: info:eu-repo/semantics/doctoralThesis type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/31721/1/Dissertation_SteffenEKuenzel_2022.pdf identifier: DOI:10.11588/heidok.00031721 identifier: urn:nbn:de:bsz:16-heidok-317211 identifier: Künzel, Steffen Emil (2022) NCK1/2 are specific mediators of migration in Pericytes and promising targets in ischemic retinopathies. [Dissertation] relation: https://archiv.ub.uni-heidelberg.de/volltextserver/31721/ rights: info:eu-repo/semantics/openAccess rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html language: eng