Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model
SEGUY, Camille
Université de Bordeaux [UB]
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Université de Bordeaux [UB]
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
JASPARD‐VINASSA, Béatrice
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
COUFFINHAL, Thierry
Département de cardiologie
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Département de cardiologie
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
DUPLAA-COUFFINHAL, Cécile
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
DUFOURCQ, Pascale
Génétique moléculaire du développement
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
< Réduire
Génétique moléculaire du développement
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
Langue
EN
Article de revue
Ce document a été publié dans
The FASEB Journal. 2020-08-14, vol. 34, n° 1, p. 1288–1303
Résumé en anglais
Retinopathies 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 ...Lire la suite >
Retinopathies 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.< Réduire
Unités de recherche