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Titolo:
Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18
Autore:
Green, ES; Rendahl, KG; Zhou, SZ; Ladner, M; Coyne, M; Srivastava, R; Manning, WC; Flannery, JG;
Indirizzi:
Univ Calif Berkeley, Dept Vis Sci, Berkeley, CA 94720 USA Univ Calif Berkeley Berkeley CA USA 94720 Vis Sci, Berkeley, CA 94720 USA Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA Univ Calif Berkeley Berkeley CA USA 94720 ll Biol, Berkeley, CA 94720 USA Chiron Corp, Emeryville, CA 94608 USA Chiron Corp Emeryville CA USA 94608Chiron Corp, Emeryville, CA 94608 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 507 - 515
SICI:
1525-0016(200104)3:4<507:TAMORD>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST-GROWTH-FACTOR; DOMINANT RETINITIS-PIGMENTOSA; TRANSGENIC RAT MODEL; ADENOASSOCIATED VIRUS; GENE-TRANSFER; ROD PHOTORECEPTORS; SURVIVAL FACTORS; IN-VIVO; EXPRESSION; RECEPTORS;
Keywords:
retinal degeneration; gene therapy; FGF-5; FGF-18; adeno-associated virus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Flannery, JG Univ Calif Berkeley, Dept Vis Sci, 360 Minor Hall, Berkeley, CA 94720 USA Univ Calif Berkeley 360 Minor Hall Berkeley CA USA 94720 USA
Citazione:
E.S. Green et al., "Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18", MOL THER, 3(4), 2001, pp. 507-515

Abstract

The goal of these experiments was to evaluate the potential of the fibroblast growth factor family members FGF-5 and FCF-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 couldameliorate 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 segments of photoreceptors, and the receptors FGFR1 and FGFR2 were also found to be upregulated in these regions. No visible pathological changes were seen in the FCF-5- or FGF-18-treated eyes. These results indicate that the delivery of either FCF-5 or FGF-18 with adenoassociated virus protects photoreceptors from apoptosisin transgenic rat models of retinitis pigmentosa and that the rescue is probably mediated by conventional receptor tyrosine kinase pathways in photoreceptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 09:59:48