{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:20:17Z","timestamp":1793334017458,"version":"4.5.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY030611 EY5722"],"award-info":[{"award-number":["EY030611 EY5722"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100002690","name":"Ruth K. Broad Biomedical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002690","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006510","name":"Duke University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006510","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Angiogenesis in the developing mammalian retina requires patterning cues from astrocytes. Developmental disorders of retinal vasculature, such as retinopathy of prematurity (ROP), involve arrest or mispatterning of angiogenesis. Whether these vascular pathologies involve astrocyte dysfunction remains untested. Here, we demonstrate that the major risk factor for ROP \u2013 transient neonatal exposure to excess oxygen \u2013 disrupts formation of the angiogenic astrocyte template. Exposing newborn mice to elevated oxygen (75%) suppressed astrocyte proliferation, whereas return to room air (21% oxygen) at postnatal day 4 triggered extensive proliferation, massively increasing astrocyte numbers and disturbing their spatial patterning prior to the arrival of developing vasculature. Proliferation required astrocytic HIF2\u03b1 and was also stimulated by direct hypoxia (10% oxygen), suggesting that astrocyte oxygen sensing regulates the number of astrocytes produced during development. Along with astrocyte defects, return to room air also caused vascular defects reminiscent of ROP. Strikingly, these vascular phenotypes were more severe in animals that had larger numbers of excess astrocytes. Together, our findings suggest that fluctuations in environmental oxygen dysregulate molecular pathways controlling astrocyte proliferation, thereby generating excess astrocytes that interfere with retinal angiogenesis.<\/jats:p>","DOI":"10.1242\/dev.199418","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T07:06:27Z","timestamp":1620371187000},"source":"Crossref","is-referenced-by-count":31,"title":["Environmental oxygen regulates astrocyte proliferation to guide angiogenesis during retinal development"],"prefix":"10.1242","volume":"148","author":[{"given":"Robin M.","family":"Perelli","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Ophthalmology Residency Program, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Zarnick","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-1604","authenticated-orcid":false,"given":"Jeremy N.","family":"Kay","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA"},{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"2022042909325276600_DEV199418C1","doi-asserted-by":"publisher","first-page":"4531","DOI":"10.1038\/sj.onc.1210249","article-title":"Loss of vascular endothelial growth factor expression reduces vascularization, but not growth, of tumors lacking the Von Hippel-Lindau tumor suppressor gene","volume":"26","author":"Blouw","year":"2007","journal-title":"Oncogene"},{"key":"2022042909325276600_DEV199418C2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.mcn.2013.06.001","article-title":"Hyperoxia causes reduced density of retinal astrocytes in the central avascular zone in the mouse model of oxygen-induced retinopathy","volume":"56","author":"Bucher","year":"2013","journal-title":"Mol. 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