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Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBATS, Marie-Lise
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBOUGARAN, Pauline
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorPEGHAIRE, Claire
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUENIOT, Florian
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorABELANET, Alice
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCHAN, Hélène
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorSEGUY, Camille
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJEANNINGROS, Sylvie
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJASPARD‐VINASSA, Béatrice
hal.structure.identifierDépartement de cardiologie
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUPLAA-COUFFINHAL, Cécile
hal.structure.identifierGénétique moléculaire du développement
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUFOURCQ, Pascale
dc.date.accessioned2020-10-19T13:40:24Z
dc.date.available2020-10-19T13:40:24Z
dc.date.issued2020-08-14
dc.identifier.issn0892-6638, 1530-6860en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/11427
dc.description.abstractEnRetinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction of anti‐angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies. However, limitations associated with anti‐VEGF medications require to unravel new pathways of vessel growth to identify potential drug targets. Here, we investigated the role of Wnt/Frizzled‐7 (Fzd7) pathway in a mouse model of oxygen‐induced retinopathy (OIR). Using transgenic mice, which enabled endothelium‐specific and time‐specific Fzd7 deletion, we demonstrated that Fzd7 controls both vaso‐obliteration and neovascular phases (NV). Deletion of Fzd7 at P12, after the ischemic phase of OIR, prevented formation of aberrant neovessels into the vitreous by suppressing proliferation of endothelial cells (EC) in tufts. Next we validated in vitro two Frd7 blocking strategies: a monoclonal antibody (mAbFzd7) against Fzd7 and a soluble Fzd7 receptor (CRD). In vivo a single intravitreal microinjection of mAbFzd7 or CRD significantly attenuated retinal neovascularization (NV) in mice with OIR. Molecular analysis revealed that Fzd7 may act through the activation of Wnt/β‐catenin and Jagged1 expression to control EC proliferation in extra‐retinal neovessels. We identified Fzd7/β‐catenin signaling as new regulator of pathological retinal NV. Fzd7 appears to be a potent pharmacological target to prevent or treat aberrant angiogenesis of ischemic retinopathies.
dc.language.isoENen_US
dc.title.enTherapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model
dc.typeArticle de revueen_US
dc.identifier.doi10.1096/fj.201901886Ren_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalThe FASEB Journalen_US
bordeaux.page1288–1303en_US
bordeaux.volume34en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=The%20FASEB%20Journal&rft.date=2020-08-14&rft.volume=34&rft.issue=1&rft.spage=1288%E2%80%931303&rft.epage=1288%E2%80%931303&rft.eissn=0892-6638,%201530-6860&rft.issn=0892-6638,%201530-6860&rft.au=BATS,%20Marie-Lise&BOUGARAN,%20Pauline&PEGHAIRE,%20Claire&GUENIOT,%20Florian&ABELANET,%20Alice&rft.genre=article


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