Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18

Molecular Therapy : the Journal of the American Society of Gene Therapy
E S GreenJ G Flannery

Abstract

The goal of these experiments was to evaluate the potential of the fibroblast growth factor family members FGF-5 and FGF-18 to rescue photoreceptors from cell death in retinal degenerative disease. Two strains of transgenic rats, expressing either a P23H or an S334ter rhodopsin mutation, were used as model systems. The neurotrophic growth factors were delivered by subretinal injection of adeno-associated virus vectors, driving expression of the genes with a constitutive CMV promoter. Morphological and functional analyses were performed to determine whether FGF-5 or FGF-18 overexpression could ameliorate cell death in the retina. Immunocytochemistry was used to determine the cellular sites of expression of the factors and to test for up-regulation of FGF receptors due to injection. Significant rescue from photoreceptor cell death was found after injections of vectors expressing either FGF-5 or FGF-18 in the animal models. Increased survival of photoreceptors did not produce a significant increase in electroretinographic responses, however, reflecting either trauma due to the surgery or a suppression of signaling due to expression of proteins. Three weeks after injections, both growth factors were localized to the inner and outer...Continue Reading

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Citations

Jul 2, 2005·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·R FriggC E Remé
Feb 24, 2011·Cell and Tissue Banking·Shuang WangYazhen Wu
Feb 8, 2003·Experimental Eye Research·Joel GatlinJames V Jester
Jul 23, 2003·Experimental Eye Research·Benoît RousseauSophie Javerzat
Oct 25, 2003·Progress in Retinal and Eye Research·Enrico M Surace, Alberto Auricchio
Nov 18, 2011·Gene Therapy·G J FarrarP F Kenna
Apr 28, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Deniz DalkaraJohn G Flannery
Jun 18, 2005·Cancer Gene Therapy·Chengwen LiRichard Jude Samulski
Apr 9, 2002·Human Gene Therapy·Andrew J LoteryBeverly L Davidson
Feb 8, 2003·DNA and Cell Biology·Chooi May LaiP Elizabeth Rakoczy
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Sep 29, 2012·Human Gene Therapy·Laura Fernández-SánchezNicolás Cuenca
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Aug 28, 2007·Vision Research·Frédéric Gaillard, Yves Sauvé
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Aug 6, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alberto AuricchioJames M Wilson
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Jan 31, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Knut StiegerFabienne Rolling
Sep 8, 2018·Investigative Ophthalmology & Visual Science·Johnny Di PierdomenicoMaría Paz Villegas-Pérez
Jan 1, 2020·Translational Vision Science & Technology·Francisco J Valiente-SorianoManuel Vidal-Sanz

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