Long-term efficacy of ciliary muscle gene transfer of three sFlt-1 variants in a rat model of laser-induced choroidal neovascularization.

Détails

ID Serval
serval:BIB_21D5F99F2B7F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Long-term efficacy of ciliary muscle gene transfer of three sFlt-1 variants in a rat model of laser-induced choroidal neovascularization.
Périodique
Gene Therapy
Auteur(s)
El Sanharawi M., Touchard E., Benard R., Bigey P., Escriou V., Mehanna C., Naud M.C., Berdugo M., Jeanny J.C., Behar-Cohen F.
ISSN
1476-5462 (Electronic)
ISSN-L
0969-7128
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
20
Pages
1093-1103
Langue
anglais
Notes
Publication types: JOURNAL ARTICLE
Résumé
Inhibition of vascular endothelial growth factor (VEGF) has become the standard of care for patients presenting with wet age-related macular degeneration. However, monthly intravitreal injections are required for optimal efficacy. We have previously shown that electroporation enabled ciliary muscle gene transfer results in sustained protein secretion into the vitreous for up to 9 months. Here, we evaluated the long-term efficacy of ciliary muscle gene transfer of three soluble VEGF receptor-1 (sFlt-1) variants in a rat model of laser-induced choroidal neovascularization (CNV). All three sFlt-1 variants significantly diminished vascular leakage and neovascularization as measured by fluorescein angiography (FA) and flatmount choroid at 3 weeks. FA and infracyanine angiography demonstrated that inhibition of CNV was maintained for up to 6 months after gene transfer of the two shortest sFlt-1 variants. Throughout, clinical efficacy was correlated with sustained VEGF neutralization in the ocular media. Interestingly, treatment with sFlt-1 induced a 50% downregulation of VEGF messenger RNA levels in the retinal pigment epithelium and the choroid. We demonstrate for the first time that non-viral gene transfer can achieve a long-term reduction of VEGF levels and efficacy in the treatment of CNV.Gene Therapy advance online publication, 27 June 2013; doi:10.1038/gt.2013.36.
Pubmed
Web of science
Création de la notice
19/08/2013 14:55
Dernière modification de la notice
20/08/2019 12:58
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