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Scopus: 27 cites, Web of Science: 22 cites,
Long-term retinal PEDF overexpression prevents neovascularization in a murine adult model of retinopathy
Haurigot Mendonça, Virginia (Centre de Biotecnologia Animal i de Teràpia Gènica)
Villacampa Alcubierre, Pilar (Centre de Biotecnologia Animal i de Teràpia Gènica)
Ribera Sánchez, Albert (Centre de Biotecnologia Animal i de Teràpia Gènica)
Bosch i Merino, Assumpció (Centre de Biotecnologia Animal i de Teràpia Gènica)
Ramos, David (Centre de Biotecnologia Animal i de Teràpia Gènica)
Ruberte París, Jesús (Centre de Biotecnologia Animal i de Teràpia Gènica)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Data: 2012
Resum: Neovascularization associated with diabetic retinopathy (DR) and other ocular disorders is a leading cause of visual impairment and adult-onset blindness. Currently available treatments are merely palliative and offer temporary solutions. Here, we tested the efficacy of antiangiogenic gene transfer in an animal model that mimics the chronic progression of human DR. Adeno-associated viral (AAV) vectors of serotype 2 coding for antiangiogenic Pigment Epithelium Derived Factor (PEDF) were injected in the vitreous of a 1. 5 month-old transgenic model of retinopathy that develops progressive neovascularization. A single intravitreal injection led to long-term production of PEDF and to a striking inhibition of intravitreal neovascularization, normalization of retinal capillary density, and prevention of retinal detachment. This was parallel to a reduction in the intraocular levels of Vascular Endothelial Growth Factor (VEGF). Normalization of VEGF was consistent with a downregulation of downstream effectors of angiogenesis, such as the activity of Matrix Metalloproteinases (MMP) 2 and 9 and the content of Connective Tissue Growth Factor (CTGF). These results demonstrate long-term efficacy of AAV-mediated PEDF overexpression in counteracting retinal neovascularization in a relevant animal model, and provides evidence towards the use of this strategy to treat angiogenesis in DR and other chronic proliferative retinal disorders.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès.
Document: article ; publishedVersion
Matèria: Animal models ; Retina ; Transgenic animals ; Capillaries ; Gene transfer
Publicat a: PLoS one, Vol. 7, Issue 7 (July 2012) , p. e41511, ISSN 1932-6203

DOI: 10.1371/journal.pone.0041511

12 p, 4.1 MB

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