
<ArticleTitle>Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis.</ArticleTitle>
<AbstractText>This report analyzes the role of <prot>vascular endothelial growth factor</prot> (<prot>VEGF</prot>)-induced angiogenesis in the immunoinflammatory lesion stromal keratitis induced by ocular infection with herpes simplex virus (HSV). Our results show that infection with replication-competent, but not mutant, viruses results in the expression of <prot>VEGF</prot> mRNA and protein in the cornea. This a rapid event, with <prot>VEGF</prot> mRNA detectable by 12 h postinfection (p.i.) and proteins detectable by 24 h p.i. <prot>VEGF</prot> production occurred both in the virus-infected corneal epithelium and in the underlying stroma, in which viral antigens were undetectable. In the stroma, <prot>VEGF</prot> was produced by inflammatory cells; these initially were predominantly polymorphonuclear leukocytes (PMN), but at later time points both PMN and macrophage-like cells were <prot>VEGF</prot> producers. In the epithelium, the major site of <prot>VEGF</prot>-expressing cells in early infection, the infected cells themselves were usually negative for <prot>VEGF</prot>. Similarly, in vitro infection studies indicated that the cells which produced <prot>VEGF</prot> were not those which expressed virus. Attesting to the possible role of <prot>VEGF</prot>-induced angiogenesis in the pathogenesis of herpetic stromal keratitis were experiments showing that <prot>VEGF</prot> inhibition with <prot>mFlt(1-3)-immunoglobulin G</prot> diminished angiogenesis and the severity of lesions after HSV infection. These observations are the first to evaluate <prot>VEGF</prot>-induced angiogenesis in the pathogenesis of stromal keratitis. Our results indicate that the control of angiogenesis represents a useful adjunct to therapy of herpetic ocular disease, an important cause of human blindness.</AbstractText>
