{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:43:46Z","timestamp":1790858626124,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,6,19]]},"abstract":"<jats:p>\n                    Vessel loss precipitates many diseases. In particular, vessel loss resulting in hypoxia induces retinal neovascularization in diabetic retinopathy and in retinopathy of prematurity (ROP), major causes of blindness. Here we define insulin-like growth factor binding protein-3 (IGFBP3) as a new modulator of vascular survival and regrowth in oxygen-induced retinopathy. In IGFBP3-deficient mice, there was a dose-dependent increase in oxygen-induced retinal vessel loss. Subsequent to oxygen-induced retinal vessel loss,\n                    <jats:italic>Igfbp3<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had a 31% decrease in retinal vessel regrowth versus controls after returning to room air. No difference in serum insulin-like growth factor 1 (IGF1) levels was observed among groups. Wild-type mice treated with exogenous IGFBP3 had a significant increase in vessel regrowth. This correlated with a 30% increase in endothelial progenitor cells in the retina at postnatal day 15, indicating that IGFBP3 could be serving as a progenitor cell chemoattractant. In a prospective clinical study, we measured IGFBP3 (and IGF1) plasma levels weekly and examined retinas in all premature infants born at gestational ages &lt;32 weeks at high risk for ROP. The mean level of IGFBP3 at 30\u201335 weeks postmenstrual age (PMA) for infants with proliferative ROP (ROP stages 3&gt;,\n                    <jats:italic>n<\/jats:italic>\n                    = 13) was 802 \u03bcg\/liter, and for infants with no ROP (ROP stage 0,\n                    <jats:italic>n<\/jats:italic>\n                    = 38) the mean level was 974 \u03bcg\/liter (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.03). These results suggest that IGFBP3, acting independently of IGF1, helps to prevent oxygen-induced vessel loss and to promote vascular regrowth after vascular destruction\n                    <jats:italic>in vivo<\/jats:italic>\n                    in a dose-dependent manner, resulting in less retinal neovascularization.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0702031104","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T00:03:28Z","timestamp":1181779408000},"page":"10589-10594","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth"],"prefix":"10.1073","volume":"104","author":[{"given":"Chatarina","family":"Lofqvist","sequence":"first","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"},{"name":"Departments of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kip M.","family":"Connor","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C. H.","family":"Smith","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Aderman","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Liu","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Pintar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute for Cancer Genetics, Department of Pathology, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hellstrom","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Sahlgrenska Academy, G\u00f6teborg University, SE-416 85 G\u00f6teborg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois E. H.","family":"Smith","sequence":"additional","affiliation":[{"name":"*Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,6,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.5.1016"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1750019"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2001-0033"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80824-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.6.1375895"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041580110"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)10384-1"},{"key":"e_1_3_4_8_2","first-page":"103","volume":"3","author":"Rocha RL","year":"1997","unstructured":"RL Rocha, SG Hilsenbeck, JG Jackson, CL VanDenBerg, C Weng, AV Lee, D Yee Clin Cancer Res 3, 103\u2013109 (1997).","journal-title":"Clin Cancer Res"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.9.601"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19981218)79:6<624::AID-IJC12>3.0.CO;2-9"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1996.523"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1618fje"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3727\/096504003108748375"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005088200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020472"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.4.6497"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10874"},{"key":"e_1_3_4_18_2","first-page":"101","volume":"35","author":"Smith LE","year":"1994","unstructured":"LE Smith, E Wesolowski, A McLellan, S. 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Kostyk, R D'Amato, R Sullivan, PA D'Amore Invest Ophthalmol Vis Sci 35, 101\u2013111 (1994).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0196"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-1926"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-861362"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2003.00921.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116877"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1993.1042"},{"key":"e_1_3_4_25_2","first-page":"11","volume":"4","author":"Blum WF","year":"1994","unstructured":"WF Blum, BH Breier Growth Reg 4, 11\u201319 (1994).","journal-title":"Growth Reg"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1490379"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702072104"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0702031104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:59:01Z","timestamp":1649779141000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0702031104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,19]]},"references-count":27,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2007,6,19]]}},"alternative-id":["10.1073\/pnas.0702031104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0702031104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6,19]]},"assertion":[{"value":"2007-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-06-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}