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Titolo:
Long-term protection of retinal structure but not function using RAAV.CNTFin animal models of retinitis pigmentosa
Autore:
Liang, FQ; Aleman, TS; Dejneka, NS; Dudus, L; Fisher, KJ; Maguire, AM; Jacobson, SG; Bennett, J;
Indirizzi:
Univ Penn, Dept Ophthalmol, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 phthalmol, Philadelphia, PA 19104 USA Tulane Univ, Med Ctr, Dept Pathol & Lab Med, New Orleans, LA 70112 USA Tulane Univ New Orleans LA USA 70112 & Lab Med, New Orleans, LA 70112 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 4, anno: 2001,
pagine: 461 - 472
SICI:
1525-0016(200111)4:5<461:LPORSB>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
CILIARY NEUROTROPHIC FACTOR; FIBROBLAST-GROWTH-FACTOR; RECOMBINANT ADENOASSOCIATED VIRUS; RDS MUTANT MICE; MULLER CELLS; POSTNATAL-DEVELOPMENT; MOUSE PHOTORECEPTORS; AXONAL REGENERATION; ROD PHOTORECEPTORS; MEDIATED DELIVERY;
Keywords:
CNTF; AAV; photoreceptor; trophic factors; retinitis pigmentosa;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Bennett, J Univ Penn, Dept Ophthalmol, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Philadelphia, PA 19104 USA
Citazione:
F.Q. Liang et al., "Long-term protection of retinal structure but not function using RAAV.CNTFin animal models of retinitis pigmentosa", MOL THER, 4(5), 2001, pp. 461-472

Abstract

The present study aimed to determine whether intravitreal administration of an adeno-associated virus (AAV) carrying ciliary neurotrophic factor (CNTF) can achieve long-term morphological and physiological rescue of photoreceptors in animal models of retinitis pigmentosa, and whether injection of this virus after degeneration begins is effective in protecting the remaining photoreceptors. We injected rAAV.CNTF.GFP intravitreally in early postnatal Prph2(Rd2/Rd2) (formerly rds/rds) mice and in adult P23H and S334ter rhodopsin transgenic rats. Contralateral eyes received an intravitreal injection of rAAV.GFP or a sham injection. We evaluated the eyes at 6 months (rats) and 8.5 to 9 months (mice) postinfection and looked for histological and electoretinographic (ERG) evidence of photoreceptor rescue and CNTF-GFP expression. Intravitreal administration of rAAV resulted in efficient transduction of retinal ganglion cells in the Prph2(Rd2/Rd2) retina, and ganglion, Muller, and horizontal/amacrine cells in the mutant rat retinas. Transgene expression localized to the retinal region closest to the injection site. We observed prominent morphological protection of photoreceptors in the eyesof all animals receiving rAAV.CNTF.GFP. We found the greatest protection in regions most distant from the CNTF-GFP-expressing cells. The Prph2(Rd2/Rd2) ERGS did not exhibit interocular differences. Eyes of the rat models administered rAAV.CNTF.GFP had lower ERG amplitudes than those receiving rAAV.GFP. The discordance of functional and structural results, especially in the rat models, points to the need for a greater understanding of the mechanism of action of CNTF before human application can be considered.

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Documento generato il 08/04/20 alle ore 09:06:54