{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:10:26Z","timestamp":1793412626983,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"14","funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01 EY024972"],"award-info":[{"award-number":["R01 EY024972"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research to Prevent Blindness Physician Scientist","award":["RPB1801"],"award-info":[{"award-number":["RPB1801"]}]},{"name":"The Hartwell Foundation Biomedical Research Fellowship","award":["HWF0609201"],"award-info":[{"award-number":["HWF0609201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,25]]},"abstract":"<jats:p>\n                    We determined which metabolic pathways are activated by hypoxia-inducible factor 1\u2013mediated (HIF-1\u2013mediated) protection against oxygen-induced retinopathy (OIR) in newborn mice, the experimental correlate to retinopathy of prematurity, a leading cause of infant blindness. HIF-1 coordinates the change from oxidative to glycolytic metabolism and mediates flux through serine and 1-carbon metabolism (1CM) in hypoxic and cancer cells. We used untargeted metabolite profiling in vivo to demonstrate that hypoxia mimesis activates serine\/1CM. Both [\n                    <jats:sup>13<\/jats:sup>\n                    C\n                    <jats:sub>6<\/jats:sub>\n                    ] glucose labeling of metabolites in ex vivo retinal explants as well as in vivo [\n                    <jats:sup>13<\/jats:sup>\n                    C\n                    <jats:sub>3<\/jats:sub>\n                    ] serine labeling of metabolites followed in liver lysates strongly suggest that retinal serine is primarily derived from hepatic glycolytic carbon and not from retinal glycolytic carbon in newborn pups. In HIF-1\u03b1\n                    <jats:sup>2lox\/2lox<\/jats:sup>\n                    albumin-Cre\u2013knockout mice, reduced or near-0 levels of serine\/glycine further demonstrate the hepatic origin of retinal serine. Furthermore, inhibition of 1CM by methotrexate blocked HIF-mediated protection against OIR. This demonstrated that 1CM participates in protection induced by HIF-1 stabilization. The urea cycle also dominated pathway enrichment analyses of plasma samples. The dependence of retinal serine on hepatic HIF-1 and the upregulation of the urea cycle emphasize the importance of the liver to remote protection of the retina.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.129398","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T11:01:07Z","timestamp":1563966067000},"source":"Crossref","is-referenced-by-count":53,"title":["Serine and 1-carbon metabolism are required for HIF-mediated protection against retinopathy of prematurity"],"prefix":"10.1172","volume":"4","author":[{"given":"Charandeep","family":"Singh","sequence":"first","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, 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