Corneal neovascularization during experimental fungal keratitis

[摘要] Purpose: To investigate the developmentof corneal neovascularization, the corneal expression of vascularendothelial growth factor (VEGF), and the antiangiogenic effects of aVEGF-inhibitory antibody during experimental keratomycosis. Methods: Scarified corneas of BALB/cmice were topically inoculated with Candidaalbicans andmonitored daily for corneal neovascularization. A murine genemicroarray compared infected corneas to controls 1 day afterinoculation. Real-time reverse transcriptase polymerase chain reaction(RT-PCR) determined levels of genes encoding VEGF-A, VEGF-B, VEGF-C,and VEGF-D and placental growth factor in infected, mock-inoculated,and normal corneas. Immunostaining localized VEGF-A in cornealsections. An anti-VEGF-A antibody that binds to murine VEGF wasevaluated for effects on corneal neovascularization and fungalrecovery. Results: Eyes with C. albicanskeratitis manifested limbal capillary budding on the secondpostinoculation day, and intrastromal neovascular tufts subsequentlygrew at a mean rate of 250±80 μm/day. One day after the onset of C.albicans keratitis, VEGF-A was upregulated 12.5 fold(p=0.01) by microarray and 8.8 fold (p=0.004) by real-time RT-PCR,followed by a measured decline toward baseline over one week. VEGF-Awas present in the epithelium and stroma of infected corneas.Scarification alone did not alter VEGF expression compared to thenormal cornea. Anti-VEGF-A antibody significantly (p<0.01) decreasedthe formation of new corneal blood vessels during experimentalkeratomycosis without adversely affecting the fungal load of C.albicans keratitis. Conclusions: Untreated C. albicanskeratitis induces VEGF-A and leads to progressive cornealneovascularization that is preventable by a VEGF-blocking antibody.

[学科分类] 生物化学/生物物理