Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization

Pathological angiogenesis, or the production of new capillary vessels from preexisting vasculature, within the eye is a serious event that often leads to blindness. Upregulation of vascular endothelial growth factor (VEGF) ha s been linked to neovascularization in the eye, suggesting that it could be a suitable target to inhibit angiogenic changes. This work investigated wh ether the presence of a proven antiangiogenic factor, the soluble variant o f the VEGF receptor, sFlt-1, in the anterior chamber is sufficient to inhib it new vessel formation in the cornea in an animal model of corneal neovasc ularization. A recombinant adenovirus vector that can mediate efficient in vivo gene transfer and expression in ocular cells was selected as a deliver y agent. We have shown that after the injection of Ad.beta gal into the ant erior chamber of normal and cauterized rat eyes, corneal endothelial cells and cells of the trabecular meshwork were efficiently transduced and that b eta -galactosidase (beta -Gal) expression was maintained up to 10 days post injection. Cauterization significantly increased the amount of immunoreacti ve VEGF in vehicle- or Ad.null-injected animals (t test, p< 0.001 and p< 0. 001, respectively). However, when cauterization was combined with Ad.sflt i njection there was no statistically significant increase in the amount of i mmunoreactive VEGF (p = 0.12). The injection of Ad.sflt into the anterior c hamber slowed or inhibited VEGF-induced angiogenic changes. After cauteriza tion, 100% of uninjected and vehicle- injected and 82% of Ad.null-injected animals developed moderate to severe corneal angiogenesis in contrast to 18 % of Ad.sflt-injected animals. These in vivo results suggest that the trans ient presence of antiangiogenic agents in the anterior chamber can be succe ssfully used to inhibit the development of corneal angiogenesis.