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S. Julien, F. Kreppel, S. Beck, S. Kochanek, M. Seeliger, U. Schraermeyer, Tuebingen Bevacizumab Study Group; Investigation of Choroidal Neovascularization in the Rat Induced by High–Capacity Adenovirus Mediated Expression of VEGF . Invest. Ophthalmol. Vis. Sci. 2006;47(13):911.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization (CNV) plays an important role in the pathogenesis of age–related macular degeneration. The purpose of this study was to induce neovascularization by injection of a high capacity adenovirus vector encoding VEGF165 (HC Ad.VEGF) into the subretinal space and to compare different detection methods of overexpression of VEGF–induced neovascularization in the rat.
A high–capacity adenoviral vector encoding VEGF was constructed and injected into the subretinal space of rats in combination with a HC Ad.EGFP which allows us to exactly localise the injection site. The development of neovascularization was followed in vivo by scanning laser ophthalmoscopy and angiography (SLO), and in vitro by electron microscopy, immunohistochemistry, fluorescein–dextran angiography, and examination of wholemounts of choroid and retina.
Fluorescein–dextran angiography of animals revealed a deep complex of new vessels in choroidal flatmounts. This observation was verified by detection of endothelial cells via immunohistochemistry in paraffin sections. Electron microscopy showed an impressive choroidal exudation but no presence of endothelial cells in the subretinal space. In SLO imaging, changes of the retinal or choroidal vascular structures in the subretinal space were not clearly discernible.
These results show that RPE–derived VEGF can induce choroidal neovascularization in the rat and may represent a relevant model to assess the effects of new therapeutic approaches since the advantages of the HC Ad.VEGF vector used are low toxicity, low immunogenicity and long–term expression of VEGF. Further work correlating SLO and histological results is in progress to address the difference in the detection of early stage CNVs. The effect of Bevacizumab (Avastin), a humanized anti–VEGF monoclonal antibody that has been recently approved as a first–line treatment for metastatic colorectal cancer, is now under investigation.
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