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Judit Baffi, Gordon Byrnes, Chi–Chao Chan, Karl G. Csaky; Choroidal Neovascularization in the Rat Induced by Adenovirus Mediated Expression of Vascular Endothelial Growth Factor. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3582-3589.
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purpose. To determine the effects of an adenovirus vector encoding vascular
endothelial growth factor165 (Ad.VEGF) delivered to the
subretinal space in the rat.
methods. An E1–deleted adenoviral vector encoding VEGF was injected
into the subretinal space of Long–Evans rats. Immunohistochemistry
identified VEGF expression. Histopathologic changes in the retina were
determined by light and electron microscopy, immunohistochemistry,
fluorescein angiography, and examination of wholemounts of choroid and
results. Increased expression of VEGF only in the retinal pigment epithelium
(RPE) was detected after Ad.VEGF injection. Histopathology of these
eyes revealed minimal subretinal exudation at 1 week followed by the
appearance of vascular structures in the subretinal space by week 2,
which persisted up to 4 weeks. Shortening of photoreceptor outer
segments and reduction of the outer nuclear layer were present
overlying areas of neovascularization. Fluorescein angiography of
animals injected with fluorescein–dextran revealed a deep complex of
new vessels. Choroidal flatmounts showed new vessel formation, verified
by detection of endothelial cells via immunohistochemistry, arising
from the choroid with absence of change in the overlying retinal
vasculature. Electron microscopy confirmed the presence of sub-RPE
endothelial cells and pericytes and the loss of integrity of Bruch’s
membrane, and serial sectioning demonstrated choroidal vascular growth
through Bruch’s membrane.
conclusions. These results support the hypothesis that overexpression of VEGF from
RPE cells is capable of inducing choroidal neovascularization in the
rat and provide a framework for further examining angiogenic processes
in the RPE–choroid complex.
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