{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:12:14Z","timestamp":1787022734543,"version":"build-2736575974"},"reference-count":56,"publisher":"Society for Neuroscience","issue":"16","license":[{"start":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T00:00:00Z","timestamp":1192665600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,4,18]]},"abstract":"<jats:p>Many diseases of the eye such as retinoblastoma, diabetic retinopathy, and retinopathy of prematurity are associated with blood\u2013retinal barrier (BRB) dysfunction. Identifying the factors that contribute to BRB formation during human eye development and maintenance could provide insights into such diseases. Here we show that A-kinase anchor protein 12 (AKAP12) induces BRB formation by increasing angiopoietin-1 and decreasing vascular endothelial growth factor (VEGF) levels in astrocytes. We reveal that AKAP12 downregulates the level of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) protein by enhancing the interaction of HIF-1\u03b1 with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2 (prolyl hydroxylase 2). Conditioned media from AKAP12-overexpressing astrocytes induced barriergenesis by upregulating the expression of tight junction proteins in human retina microvascular endothelial cells (HRMECs). Compared with the retina during BRB maturation, AKAP12 expression in retinoblastoma patient tissue was markedly reduced whereas that of VEGF was increased. These findings suggest that AKAP12 may induce BRB formation through antiangiogenesis and barriergenesis in the developing human eye and that defects in this mechanism can lead to a loss of tight junction proteins and contribute to the development of retinal pathologies such as retinoblastoma.<\/jats:p>","DOI":"10.1523\/jneurosci.5368-06.2007","type":"journal-article","created":{"date-parts":[[2007,4,18]],"date-time":"2007-04-18T12:48:03Z","timestamp":1176900483000},"page":"4472-4481","source":"Crossref","is-referenced-by-count":90,"title":["AKAP12 Regulates Human Blood\u2013Retinal Barrier Formation by Downregulation of Hypoxia-Inducible Factor-1\u03b1"],"prefix":"10.1523","volume":"27","author":[{"given":"Yoon Kyung","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jean","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae-Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Kwan","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hum","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Suk","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Won","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,4,18]]},"reference":[{"key":"2023041303245863000_27.16.4472.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"2023041303245863000_27.16.4472.2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406026200"},{"key":"2023041303245863000_27.16.4472.3","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg392"},{"key":"2023041303245863000_27.16.4472.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.12.123"},{"key":"2023041303245863000_27.16.4472.5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00360.2003"},{"key":"2023041303245863000_27.16.4472.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.31.19482"},{"key":"2023041303245863000_27.16.4472.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307575101"},{"key":"2023041303245863000_27.16.4472.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81812-7"},{"key":"2023041303245863000_27.16.4472.9","first-page":"97","article-title":"Vascular permeability factor\/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis","volume":"237","author":"Dvorak","year":"1999","journal-title":"Curr Top Microbiol Immunol"},{"key":"2023041303245863000_27.16.4472.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4273"},{"key":"2023041303245863000_27.16.4472.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0751-z"},{"key":"2023041303245863000_27.16.4472.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00507-4"},{"key":"2023041303245863000_27.16.4472.13","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.127.6.1617"},{"key":"2023041303245863000_27.16.4472.14","doi-asserted-by":"publisher","DOI":"10.2741\/gelman"},{"key":"2023041303245863000_27.16.4472.15","doi-asserted-by":"publisher","DOI":"10.1023\/A:1003950027529"},{"key":"2023041303245863000_27.16.4472.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02343.x"},{"key":"2023041303245863000_27.16.4472.17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.34.19761"},{"key":"2023041303245863000_27.16.4472.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059817"},{"key":"2023041303245863000_27.16.4472.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059796"},{"key":"2023041303245863000_27.16.4472.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00038-0"},{"key":"2023041303245863000_27.16.4472.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61115-7"},{"key":"2023041303245863000_27.16.4472.22","first-page":"1075","article-title":"Intermediate filaments in the human retina and retinoblastoma. An immunohistochemical study of vimentin, glial fibrillary acidic protein, and neurofilaments","volume":"27","author":"Kivela","year":"1986","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023041303245863000_27.16.4472.23","first-page":"3290","article-title":"Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models","volume":"61","author":"Lee","year":"2001","journal-title":"Cancer Res"},{"key":"2023041303245863000_27.16.4472.24","doi-asserted-by":"publisher","DOI":"10.1038\/nm889"},{"key":"2023041303245863000_27.16.4472.25","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0177(20010201)220:2<175::AID-DVDY1101>3.0.CO;2-F"},{"key":"2023041303245863000_27.16.4472.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28430"},{"key":"2023041303245863000_27.16.4472.27","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-105"},{"key":"2023041303245863000_27.16.4472.28","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3293"},{"key":"2023041303245863000_27.16.4472.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.15.8104"},{"key":"2023041303245863000_27.16.4472.30","doi-asserted-by":"publisher","DOI":"10.1038\/20459"},{"key":"2023041303245863000_27.16.4472.31","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90573-9"},{"key":"2023041303245863000_27.16.4472.32","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0153fje"},{"key":"2023041303245863000_27.16.4472.33","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011982906125"},{"key":"2023041303245863000_27.16.4472.34","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302230"},{"key":"2023041303245863000_27.16.4472.35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7543"},{"key":"2023041303245863000_27.16.4472.36","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1242\/jcs.112.3.361","article-title":"Involvement of the protein kinase C substrate, SSeCKS, in the actin-based stellate morphology of mesangial cells","volume":"112","author":"Nelson","year":"1999","journal-title":"J Cell Sci"},{"key":"2023041303245863000_27.16.4472.37","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302070"},{"key":"2023041303245863000_27.16.4472.38","doi-asserted-by":"crossref","first-page":"C1066","DOI":"10.1152\/ajpcell.1999.277.6.C1066","article-title":"Hypoxia\/aglycemia increases endothelial permeability: role of second messengers and cytoskeleton","volume":"277","author":"Park","year":"1999","journal-title":"Am J Physiol"},{"key":"2023041303245863000_27.16.4472.39","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(01)00012-X"},{"key":"2023041303245863000_27.16.4472.40","first-page":"2408","article-title":"VEGF-initiated blood-retinal barrier breakdown in early diabetes","volume":"42","author":"Qaum","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2023041303245863000_27.16.4472.41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22642"},{"key":"2023041303245863000_27.16.4472.42","unstructured":"Sambrook J Russell D (2001) Molecular Cloning: a laboratory manuel (Cold Spring Harbor, New York)."},{"key":"2023041303245863000_27.16.4472.43","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10705"},{"key":"2023041303245863000_27.16.4472.44","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1187"},{"key":"2023041303245863000_27.16.4472.45","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6205"},{"key":"2023041303245863000_27.16.4472.46","first-page":"481","article-title":"A dynamic model of the blood-brain barrier \u201cin vitro\u201d","volume":"17","author":"Stanness","year":"1996","journal-title":"Neurotoxicology"},{"key":"2023041303245863000_27.16.4472.47","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(1998110)186:3<306::AID-PATH183>3.0.CO;2-B"},{"key":"2023041303245863000_27.16.4472.48","doi-asserted-by":"crossref","first-page":"4738","DOI":"10.1523\/JNEUROSCI.15-07-04738.1995","article-title":"Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia","volume":"15","author":"Stone","year":"1995","journal-title":"J Neurosci"},{"key":"2023041303245863000_27.16.4472.49","doi-asserted-by":"publisher","DOI":"10.1038\/74725"},{"key":"2023041303245863000_27.16.4472.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5510"},{"key":"2023041303245863000_27.16.4472.51","doi-asserted-by":"crossref","first-page":"H434","DOI":"10.1152\/ajpheart.2001.280.1.H434","article-title":"VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly","volume":"280","author":"Wang","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2023041303245863000_27.16.4472.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2004.07.006"},{"key":"2023041303245863000_27.16.4472.53","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01732"},{"key":"2023041303245863000_27.16.4472.54","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00043-5"},{"key":"2023041303245863000_27.16.4472.55","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1527"},{"key":"2023041303245863000_27.16.4472.56","first-page":"5644","article-title":"The Src-suppressed C kinase substrate, SSeCKS, is a potential metastasis inhibitor in prostate cancer","volume":"61","author":"Xia","year":"2001","journal-title":"Cancer Res"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.5368-06.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T13:58:16Z","timestamp":1681394296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.5368-06.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,18]]},"references-count":56,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2007,4,18]]},"published-print":{"date-parts":[[2007,4,18]]}},"alternative-id":["10.1523\/JNEUROSCI.5368-06.2007"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.5368-06.2007","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,18]]}}}