{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:47:18Z","timestamp":1793195238547,"version":"4.5.0"},"reference-count":56,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"10","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2024,8,21]]},"DOI":"10.1167\/iovs.65.10.27","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T18:45:18Z","timestamp":1724265918000},"page":"27","source":"Crossref","is-referenced-by-count":4,"title":["Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons"],"prefix":"10.1167","volume":"65","author":[{"given":"Jie","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, PLA Army General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Scheer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Lange","sequence":"additional","affiliation":[{"name":"Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"B\u00fcrger","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Rothemund","sequence":"additional","affiliation":[{"name":"Core Unit Peptide Technologies, Medical Faculty, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruaa","family":"Younis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan D.","family":"Unterlauft","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital, Inselspital, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Eichler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1016\/S2214-109X(17)30393-5","article-title":"Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis","volume":"5","author":"Flaxman","year":"2017","journal-title":"Lancet Glob Health"},{"key":"bib2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1350-9462(98)00014-7","article-title":"Neuronal death in glaucoma","volume":"18","author":"Quigley","year":"1999","journal-title":"Prog Retin Eye Res"},{"key":"bib3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0278-5846(03)00023-X","article-title":"A new view of diabetic retinopathy: a neurodegenerative disease of the eye","volume":"27","author":"Barber","year":"2003","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"bib4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.preteyeres.2011.11.002","article-title":"The molecular basis of retinal ganglion cell death in glaucoma","volume":"31","author":"Almasieh","year":"2012","journal-title":"Prog Retin Eye Res"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1167\/iovs.12-9483h","article-title":"The cell and molecular biology of glaucoma: mechanisms of retinal ganglion cell death","volume":"53","author":"Nickells","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib6","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1167\/iovs.10-6293","article-title":"The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy","volume":"52","author":"Barber","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib7","doi-asserted-by":"crossref","first-page":"E2655","DOI":"10.1073\/pnas.1522014113","article-title":"Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus","volume":"113","author":"Sohn","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.preteyeres.2003.12.001","article-title":"Retinal ischemia: mechanisms of damage and potential therapeutic strategies","volume":"23","author":"Osborne","year":"2004","journal-title":"Prog Retin Eye Res"},{"key":"bib9","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.exer.2010.04.002","article-title":"Mechanisms of retinal ganglion cell injury and defense in glaucoma","volume":"91","author":"Qu","year":"2010","journal-title":"Exp Eye Res"},{"key":"bib10","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1007\/s11064-012-0747-8","article-title":"Pigment epithelium-derived factor released by M\u00fcller glial cells exerts neuroprotective effects on retinal ganglion cells","volume":"37","author":"Unterlauft","year":"2012","journal-title":"Neurochem Res"},{"key":"bib11","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.exer.2014.08.004","article-title":"Enhanced survival of retinal ganglion cells is mediated by M\u00fcller glial cell-derived PEDF","volume":"127","author":"Unterlauft","year":"2014","journal-title":"Exp Eye Res"},{"key":"bib12","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1076\/ceyr.22.4.245.5506","article-title":"Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury","volume":"22","author":"Ogata","year":"2001","journal-title":"Curr Eye Res"},{"key":"bib13","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1167\/iovs.03-0052","article-title":"Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor","volume":"44","author":"Takita","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2202-8-11","article-title":"Pigment epithelium-derived factor protects retinal ganglion cells","volume":"8","author":"Pang","year":"2007","journal-title":"BMC Neurosci"},{"key":"bib15","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1167\/iovs.13-11803","article-title":"Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury","volume":"54","author":"Vigneswara","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib16","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.mcn.2015.08.001","article-title":"Eye drop delivery of pigment epithelium-derived factor-34 promotes retinal ganglion cell neuroprotection and axon regeneration","volume":"68","author":"Vigneswara","year":"2015","journal-title":"Mol Cell Neurosci"},{"key":"bib17","first-page":"438","article-title":"Anti-inflammatory effect of pigment epithelium-derived factor in DBA\/2J mice","volume":"15","author":"Zhou","year":"2009","journal-title":"Mol Vis"},{"key":"bib18","doi-asserted-by":"crossref","first-page":"25241","DOI":"10.1074\/jbc.M115.645846","article-title":"Small retinoprotective peptides reveal a receptor-binding region on pigment epithelium-derived factor","volume":"290","author":"Kenealey","year":"2015","journal-title":"J Biol Chem"},{"key":"bib19","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.preteyeres.2004.05.002","article-title":"Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential","volume":"23","author":"Barnstable","year":"2004","journal-title":"Prog Retin Eye Res"},{"key":"bib20","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1096\/fj.05-4313fje","article-title":"Pigment epithelium-derived factor (PEDF) is an endogenous antiinflammatory factor","volume":"20","author":"Zhang","year":"2006","journal-title":"FASEB J"},{"key":"bib21","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.ajpath.2010.10.014","article-title":"Overexpression of pigment epithelium-derived factor inhibits retinal inflammation and neovascularization","volume":"178","author":"Park","year":"2011","journal-title":"Am J Pathol"},{"key":"bib22","doi-asserted-by":"crossref","first-page":"12439","DOI":"10.1523\/JNEUROSCI.0434-06.2006","article-title":"Human vascular endothelial growth factor protects axotomized retinal ganglion cells in vivo by activating ERK-1\/2 and Akt pathways","volume":"26","author":"Kilic","year":"2006","journal-title":"J Neurosci"},{"key":"bib23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2353\/ajpath.2007.061237","article-title":"Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury","volume":"171","author":"Nishijima","year":"2007","journal-title":"Am J Pathol"},{"key":"bib24","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.ajpath.2012.12.032","article-title":"VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma","volume":"182","author":"Foxton","year":"2013","journal-title":"Am J Pathol"},{"key":"bib25","doi-asserted-by":"crossref","first-page":"102378","DOI":"10.1016\/j.jbc.2022.102378","article-title":"Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity","volume":"298","author":"Murata","year":"2022","journal-title":"J Biol Chem"},{"key":"bib26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/jnr.23316","article-title":"Protective effects of placental growth factor on retinal neuronal cell damage","volume":"92","author":"Inoue","year":"2014","journal-title":"J Neurosci Res"},{"key":"bib27","doi-asserted-by":"crossref","first-page":"25646","DOI":"10.1016\/S0021-9258(18)47298-5","article-title":"Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1\/KDR","volume":"269","author":"Park","year":"1994","journal-title":"J Biol Chem"},{"key":"bib28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/88842","article-title":"Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration","volume":"28","author":"Oosthuyse","year":"2001","journal-title":"Nat Genet"},{"key":"bib29","doi-asserted-by":"crossref","first-page":"10242","DOI":"10.1073\/pnas.97.18.10242","article-title":"Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia","volume":"97","author":"Jin","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/sj.onc.1201545","article-title":"Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1","volume":"16","author":"Landgren","year":"1998","journal-title":"Oncogene"},{"key":"bib31","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":"bib32","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1097\/00001756-200011090-00026","article-title":"VEGF release by retinal glia depends on both oxygen and glucose supply","volume":"11","author":"Eichler","year":"2000","journal-title":"Neuroreport"},{"key":"bib33","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.febslet.2005.01.017","article-title":"Upregulation of placental growth factor by vascular endothelial growth factor via a post-transcriptional mechanism","volume":"579","author":"Yao","year":"2005","journal-title":"FEBS Lett"},{"key":"bib34","first-page":"4","article-title":"The golden age of retinal cell culture","volume":"5","author":"Seigel","year":"1999","journal-title":"Mol Vis"},{"key":"bib35","first-page":"2","article-title":"Expression of glial markers in a retinal precursor cell line","volume":"2","author":"Seigel","year":"1996","journal-title":"Mol Vis"},{"key":"bib36","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1159\/000485537","article-title":"M\u00fcller cell-derived PEDF mediates neuroprotection via STAT3 activation","volume":"44","author":"Eichler","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"bib37","first-page":"1138","article-title":"Use of peptide libraries to map the substrate specificity of a peptide-modifying enzyme: a 13 residue consensus peptide specifies biotinylation in Escherichia coli","volume":"11","author":"Schatz","year":"1993","journal-title":"Biotechnology (N Y)"},{"key":"bib38","doi-asserted-by":"crossref","first-page":"9217","DOI":"10.1016\/S0040-4020(01)85612-X","article-title":"Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support","volume":"48","author":"Frank","year":"1992","journal-title":"Tetrahedron"},{"key":"bib39","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/S0006-291X(02)00548-X","article-title":"Pigment epithelium-derived factor exerts opposite effects on endothelial cells of different phenotypes","volume":"294","author":"Hutchings","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"bib40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/jme.1.02008","article-title":"Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy","volume":"37","author":"Zhang","year":"2006","journal-title":"J Mol Endocrinol"},{"key":"bib41","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1074\/jbc.M507401200","article-title":"Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1","volume":"281","author":"Cai","year":"2006","journal-title":"J Biol Chem"},{"key":"bib42","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00125-006-0539-2","article-title":"Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy","volume":"50","author":"Miyamoto","year":"2007","journal-title":"Diabetologia"},{"key":"bib43","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S0002-9394(01)01008-X","article-title":"Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy and high in rhegmatogenous retinal detachment","volume":"132","author":"Ogata","year":"2001","journal-title":"Am J Ophthalmol"},{"key":"bib44","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.ajo.2003.11.080","article-title":"Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases","volume":"137","author":"Ogata","year":"2004","journal-title":"Am J Ophthalmol"},{"key":"bib45","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0002-9394(14)75794-0","article-title":"Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy","volume":"118","author":"Adamis","year":"1994","journal-title":"Am J Ophthalmol"},{"key":"bib46","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJM199412013312203","article-title":"Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders","volume":"331","author":"Aiello","year":"1994","journal-title":"N Engl J Med"},{"key":"bib47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3390\/ijms22010369","article-title":"Pigment epithelium-derived factor (PEDF) receptors are involved in survival of retinal neurons","volume":"22","author":"B\u00fcrger","year":"2020","journal-title":"Int J Mol Sci"},{"key":"bib48","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/nm.1873","article-title":"The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis","volume":"14","author":"Sapieha","year":"2008","journal-title":"Nat Med"},{"key":"bib49","doi-asserted-by":"crossref","first-page":"10382","DOI":"10.1074\/jbc.272.16.10382","article-title":"Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1","volume":"272","author":"Barleon","year":"1997","journal-title":"J Biol Chem"},{"key":"bib50","doi-asserted-by":"crossref","first-page":"10382","DOI":"10.1074\/jbc.M313237200","article-title":"The crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1","volume":"279","author":"Christinger","year":"2004","journal-title":"J Biol Chem"},{"key":"bib51","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.str.2016.12.012","article-title":"Structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A","volume":"25","author":"Markovic-Mueller","year":"2017","journal-title":"Structure"},{"key":"bib52","doi-asserted-by":"crossref","first-page":"38022","DOI":"10.1074\/jbc.M600353200","article-title":"Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor","volume":"281","author":"Notari","year":"2006","journal-title":"J Biol Chem"},{"key":"bib53","doi-asserted-by":"crossref","first-page":"10480","DOI":"10.1074\/jbc.M809259200","article-title":"Laminin receptor involvement in the anti-angiogenic activity of pigment epithelium-derived factor","volume":"284","author":"Bernard","year":"2009","journal-title":"J Biol Chem"},{"key":"bib54","first-page":"1359","article-title":"The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy","volume":"152","author":"Stitt","year":"1998","journal-title":"Am J Pathol"},{"key":"bib55","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/87904","article-title":"Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions","volume":"7","author":"Carmeliet","year":"2001","journal-title":"Nat Med"},{"key":"bib56","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cell.2010.02.039","article-title":"Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease","volume":"141","author":"Van de Veire","year":"2010","journal-title":"Cell"}],"container-title":["Investigative Ophthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2800702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:51Z","timestamp":1791927111000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2800702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,21]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,8,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.10.27","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,8,21]]}}}