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Titolo:
Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization
Autore:
Lai, CM; Brankkov, M; Zaknich, T; Lai, YKY; Shen, WY; Constable, IJ; Kovesdi, I; Rakoczy, PE;
Indirizzi:
QE II Med Ctr, Lions Eye Inst, Nedlands, WA 6009, Australia QE II Med CtrNedlands WA Australia 6009 st, Nedlands, WA 6009, Australia Univ Western Australia, Ctr Ophthalmol & Visual Sci, Nedlands, WA 6009, Australia Univ Western Australia Nedlands WA Australia 6009 nds, WA 6009, Australia GenVec Inc, Gaithersburg, MD 20878 USA GenVec Inc Gaithersburg MD USA 20878 nVec Inc, Gaithersburg, MD 20878 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 10, volume: 12, anno: 2001,
pagine: 1299 - 1310
SICI:
1043-0342(200107)12:10<1299:IOABAS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; PROLIFERATIVE DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS; RETINAL NEOVASCULARIZATION; FACTOR RECEPTOR; GENE-TRANSFER; MACULAR DEGENERATION; TUMOR-GROWTH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Rakoczy, PE QE II Med Ctr, Lions Eye Inst, 2 Verdun St, Nedlands, WA 6009,Australia QE II Med Ctr 2 Verdun St Nedlands WA Australia 6009 Australia
Citazione:
C.M. Lai et al., "Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization", HUM GENE TH, 12(10), 2001, pp. 1299-1310

Abstract

Pathological angiogenesis, or the production of new capillary vessels frompreexisting vasculature, within the eye is a serious event that often leads to blindness. Upregulation of vascular endothelial growth factor (VEGF) has been linked to neovascularization in the eye, suggesting that it could be a suitable target to inhibit angiogenic changes. This work investigated whether the presence of a proven antiangiogenic factor, the soluble variant of the VEGF receptor, sFlt-1, in the anterior chamber is sufficient to inhibit new vessel formation in the cornea in an animal model of corneal neovascularization. A recombinant adenovirus vector that can mediate efficient invivo gene transfer and expression in ocular cells was selected as a delivery agent. We have shown that after the injection of Ad.beta gal into the anterior chamber of normal and cauterized rat eyes, corneal endothelial cellsand cells of the trabecular meshwork were efficiently transduced and that beta -galactosidase (beta -Gal) expression was maintained up to 10 days postinjection. Cauterization significantly increased the amount of immunoreactive VEGF in vehicle- or Ad.null-injected animals (t test, p< 0.001 and p< 0.001, respectively). However, when cauterization was combined with Ad.sflt injection there was no statistically significant increase in the amount of immunoreactive VEGF (p = 0.12). The injection of Ad.sflt into the anterior chamber slowed or inhibited VEGF-induced angiogenic changes. After cauterization, 100% of uninjected and vehicle- injected and 82% of Ad.null-injectedanimals developed moderate to severe corneal angiogenesis in contrast to 18% of Ad.sflt-injected animals. These in vivo results suggest that the transient presence of antiangiogenic agents in the anterior chamber can be successfully used to inhibit the development of corneal angiogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/08/20 alle ore 19:55:06