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U. Schraermeyer, F. Kreppel, S. Beck, P. Heiduschka, M. Völker, S. Kochanek, S. Julien; A Reproducible and Quantifiable Model of Choroidal Neovascularization Induced by Vegf a or D After Subretinal Adenoviral Gene Transfer in the Rabbit. Invest. Ophthalmol. Vis. Sci. 2008;49(13):852.
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To determine the effects of the vascular endothelial growth factor (VEGF)-A165 and (VEGF)-D ΔNΔC delivered using high capacity adenoviral vectors (HC Ad.VEGF-A) and (HC Ad.VEGF-DΔNΔC) on vascular growth and pathological changes in the rabbit eye and to combine different detection methods of VEGF's overexpression-induced neovascularization in the rabbit.
HC Ad.VEGF-A165 and HC Ad.VEGF-D ΔNΔC were constructed and separately injected at 5x106 infectious units into the subretinal space of rabbit eyes. The development of neovascularization and the expression of HC Ad-transduced VEGF proteins were followed up in vivo by scanning laser ophthalmoscopy, and fluorescein and indocyanine green angiographies and ex vivo by electron microscopy and immunohistochemistry four weeks after the injection.
After injection of both vectors, we observed choroidal neovascularization (CNV) with leakage in rabbit eyes. Our findings present clear indications that there is a significant effect on the endothelial cells of the choriocapillaris after the subretinal transduction of the retinal pigment epithelium (RPE) with VEGF vectors. The choroidal endothelial cells are activated, endothelial junctions open, the fenestration is minimised, while the endothelial cells augment the extracellular matrix, begin to migrate and infiltrate the Bruch’s membrane at the same time. They also proliferate and form pathological vessels in the subretinal space. Moreover, an increased expression of FGF and VEGF-A+D accompanied with stimulation of macrophages, retinal oedema and loss of photoreceptors were observed.
This is the first model of VEGF A or D induced CNV in the rabbit, in which the pathological events following overexpression of VEGF's by RPE cells have been described in details. Many of the features of our experimental CNV resemble those observed clinically in patients suffering from wet age-related macular degeneration.
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