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Diabetes ; 52(3): 857-63, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12606531

RESUMEN

Diabetic retinopathy, one of the most serious complications of long-term diabetes, could clinically be divided into two stages: 1) background retinopathy that does not cause visual impairment and 2) proliferative retinopathy, which is a potentially blinding condition. This study aims to investigate the correlation between enhancement of vascular endothelial growth factor (VEGF) expression and neovascular changes. A binary recombinant adeno-associated virus construct producing green fluorescent protein (GFP) and VEGF under the control of the human cytomegalovirus promoter, recombinant adeno-associated virus (rAAV).VEGF.GFP, was produced and injected into the subretinal space of C57BL mice. GFP expression was tracked by fluorescence fundus photography, and VEGF expression was confirmed by immunohistochemistry and enzyme-linked immunoassay. Neovascular changes were monitored by fluorescein angiography and histology and by quantifying the number of inner retinal vessels. GFP expression was found in 100% of injected eyes, and vascular changes were detected in 9 of 10 rAAV.VEGF.GFP-injected eyes. Of these, four demonstrated microaneurysms and five showed moderate to severe leakage. There was a statistically significant increase in blood vessel number in the inner nuclear layer (P < 0.03) and dilatation of retinal veins (P < or = 0.05). This work has demonstrated that the development of different stages of diabetic retinopathy is closely correlated with an increased VEGF level in the retina.


Asunto(s)
Dependovirus/genética , Retinopatía Diabética , Modelos Animales de Enfermedad , Factores de Crecimiento Endotelial/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Linfocinas/genética , Retina/metabolismo , Animales , Citomegalovirus/genética , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Factores de Crecimiento Endotelial/análisis , Ensayo de Inmunoadsorción Enzimática , Angiografía con Fluoresceína , Expresión Génica , Vectores Genéticos , Proteínas Fluorescentes Verdes , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intercelular/análisis , Proteínas Luminiscentes/genética , Linfocinas/análisis , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Proteínas Recombinantes de Fusión , Retina/química , Vasos Retinianos/patología , Vasos Retinianos/fisiopatología , Transfección , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Vasodilatación
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