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dc.contributor.authorQin, Yaowu
dc.contributor.authorZhang, Jing
dc.contributor.authorBabapoor-Farrokhran, Savalan
dc.contributor.authorApplewhite, Brooks
dc.contributor.authorDeshpande, Monika
dc.contributor.authorMegarity, Haley
dc.contributor.authorFlores-Bellver, Miguel
dc.contributor.authorAparicio-Domingo, Silvia
dc.contributor.authorMa, Tao
dc.contributor.authorRui, Yuan
dc.contributor.authorTzeng, Stephany Y
dc.contributor.authorGreen, Jordan J
dc.contributor.authorCanto-Soler, M Valeria
dc.contributor.authorMontaner, Silvia
dc.contributor.authorSodhi, Akrit
dc.date.accessioned2022-03-14T12:43:18Z
dc.date.available2022-03-14T12:43:18Z
dc.date.issued2022-03-02
dc.identifier.urihttp://hdl.handle.net/10713/18221
dc.description.abstractFor patients with proliferative diabetic retinopathy (PDR) who do not respond adequately to pan-retinal laser photocoagulation (PRP) or anti-vascular endothelial growth factor (VEGF) therapies, we hypothesized that vascular cells within neovascular tissue secrete autocrine/paracrine angiogenic factors that promote disease progression. To identify these factors, we performed multiplex ELISA angiogenesis arrays on aqueous fluid from PDR patients who responded inadequately to anti-VEGF therapy and/or PRP and identified plasminogen activator inhibitor-1 (PAI-1). PAI-1 expression was increased in vitreous biopsies and neovascular tissue from PDR eyes, limited to retinal vascular cells, regulated by the transcription factor hypoxia-inducible factor (HIF)-2α, and necessary and sufficient to stimulate angiogenesis. Using a pharmacologic inhibitor of HIF-2α (PT-2385) or nanoparticle-mediated RNA interference targeting Pai1, we demonstrate that the HIF-2α/PAI-1 axis is necessary for the development of retinal neovascularization in mice. These results suggest that targeting HIF-2α/PAI-1 will be an effective adjunct therapy for the treatment of PDR patients.en_US
dc.description.urihttps://doi.org/10.1126/sciadv.abm1896en_US
dc.language.isoenen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.ispartofScience Advancesen_US
dc.titlePAI-1 is a vascular cell-specific HIF-2-dependent angiogenic factor that promotes retinal neovascularization in diabetic patients.en_US
dc.typeArticleen_US
dc.identifier.doi10.1126/sciadv.abm1896
dc.identifier.pmid35235351
dc.source.journaltitleScience advances
dc.source.volume8
dc.source.issue9
dc.source.beginpageeabm1896
dc.source.endpage
dc.source.countryUnited States


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