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Titolo:
INTRAVITREAL SUSTAINED-RELEASE OF VEGF CAUSES RETINAL NEOVASCULARIZATION IN RABBITS AND BREAKDOWN OF THE BLOOD-RETINAL BARRIER IN RABBITS AND PRIMATES
Autore:
OZAKI H; HAYASHI H; VINORES SA; MOROMIZATO Y; CAMPOCHIARO PA; OSHIMA K;
Indirizzi:
JOHNS HOPKINS SCH MED,WILMER EYE INST,MAUMENEE 719,600 N WOLFE ST BALTIMORE MD 21287 FUKUOKA UNIV,SCH MED,DEPT OPHTHALMOL FUKUOKA 81401 JAPAN JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL BALTIMORE MD 21205 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI BALTIMORE MD 21205
Titolo Testata:
Experimental Eye Research
fascicolo: 4, volume: 64, anno: 1997,
pagine: 505 - 517
SICI:
0014-4835(1997)64:4<505:ISOVCR>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; OXYGEN-INDUCED RETINOPATHY; VASOPROLIFERATIVE MICROANGIOPATHY; IMMUNOHISTOCHEMICAL LOCALIZATION; TUMOR ANGIOGENESIS; MINIATURE PIGS; TISSUE HYPOXIA; SERUM-ALBUMIN;
Keywords:
BLOOD-RETINAL BARRIER; ISCHEMIC RETINOPATHIES; MACULAR EDEMA; RETINAL NEOVASCULARIZATION; VASCULAR ENDOTHELIAL GROWTH FACTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
H. Ozaki et al., "INTRAVITREAL SUSTAINED-RELEASE OF VEGF CAUSES RETINAL NEOVASCULARIZATION IN RABBITS AND BREAKDOWN OF THE BLOOD-RETINAL BARRIER IN RABBITS AND PRIMATES", Experimental Eye Research, 64(4), 1997, pp. 505-517

Abstract

Vascular endothelial growth factor (VEGF) has been identified as a possible mediator of retinal neooascularization (NV), but it is not certain if VEGF alone is sufficient to cause retinal NV. We sought to investigate this issue by implanting ethylene-vinyl acetate copolymer pellets that slowly release VEGF into the vitreous cavity of rabbits and primates. Eyes were examined by indirect ophthalmoscopy, fundus photography, and fluorescein angiography and then animals were killed at various time points and immunocytochemical and ultrastructural evaluationswere carried out. Seven days after implantation of a pellet containing 30 mu g of human recombinant VEGP into the vitreous cavity of rabbits, retinal blood vessels became dilated and tortuous, and between days14 and 21, retinal NV was noted in all eyes. Fluorescein angiography showed profuse leakage of dye from the anomalous vessels. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) showed positively staining nuclei in many of the endothelial cells of new blood vessels on the surface of the retina. Six eyes implanted with control pellets containing vehicle and two eyes implanted with pellets containing 30 mu g of human serum albumin alone showed no retinal Vascularabnormalities. Implantation of pellets containing 100 mu g of VEGF into the vitreous cavity of primates resulted in iris NV and retinal vascular dilation and tortuosity very much like that seen in humans with ischemic retinopathies. Immunohistochemical staining for serum albuminshowed widespread severe breakdown of the blood-retinal barrier (BRB). Histology showed dilated thin-walled retinal vessels, but unequivocal retinal NV could not be identified and staining for PCNA was negative. These findings indicate that sustained intravitreal release of VEGFcauses widespread retinal vascular dilation and breakdown of the BRB. Retinal NV seems to require persistent high levels of VEGF at the retinal surface and can be achieved in rabbits providing a potentially useful model of retinal NV, but is difficult to achieve in primates. Theextensive VEGF-induced disruption of the blood-retinal barrier suggests that VEGF antagonists may provide a new therapy for patients with ischemic retinopathies and macular edema. (C) 1997 Academic Press Limited.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:33:42