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However, in adulthood, disrupted endothelial-pericyte interactions lead to vascular dropout and pathological angiogenesis in ocular microvascular diseases, and strategies to stabilize the retinal vasculature are lacking. We demonstrate that direct endothelial-pericyte contact downregulates pVEGFR2 in endothelial cells, which enhances pericyte migration and promotes endothelial cell barrier function. Intravitreal injection of a VEGFR2 inhibitor in mouse models of the developing retina and oxygen-induced retinopathy increased pericyte recruitment and aided vascular stability. The VEGFR2 inhibitor further rescued ischemic retinopathy by enhancing vascularization and tissue growth while reducing vascular permeability. Our findings offer a druggable target to support the growth of functional and mature microvasculature in ocular microvascular diseases and tissue regeneration overall.<\/jats:p>","DOI":"10.1101\/2025.03.08.642174","type":"posted-content","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T06:50:39Z","timestamp":1741675839000},"source":"Crossref","is-referenced-by-count":1,"title":["Endothelial-pericyte interactions regulate angiogenesis via VEGFR2 signaling during retinal development and disease"],"prefix":"10.64898","author":[{"given":"Ying-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA"},{"name":"Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5839-0222","authenticated-orcid":false,"given":"Emily","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bria L.","family":"Macklin","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Gerecht","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041112562487000_2025.03.08.642174v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjopt.2018.05.002"},{"key":"2026041112562487000_2025.03.08.642174v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/diabetology3010011"},{"key":"2026041112562487000_2025.03.08.642174v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.021"},{"key":"2026041112562487000_2025.03.08.642174v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.02.017"},{"key":"2026041112562487000_2025.03.08.642174v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad348"},{"key":"2026041112562487000_2025.03.08.642174v1.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609048200"},{"key":"2026041112562487000_2025.03.08.642174v1.7","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314517"},{"key":"2026041112562487000_2025.03.08.642174v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.415"},{"key":"2026041112562487000_2025.03.08.642174v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"2026041112562487000_2025.03.08.642174v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102246"},{"key":"2026041112562487000_2025.03.08.642174v1.11","first-page":"526","article-title":"Erythropoietin deficiency decreases vascular stability in mice","volume":"118","year":"2008","journal-title":"The Journal of clinical investigation"},{"key":"2026041112562487000_2025.03.08.642174v1.12","doi-asserted-by":"crossref","unstructured":"Cho H , Macklin BL , Lin Y-Y , Zhou L , Lai MJ , Lee G , Gerecht S , Duh EJ (2020) iPSC-derived endothelial cell response to hypoxia via SDF1a\/CXCR4 axis facilitates incorporation to revascularize ischemic retina. 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