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X. Yuan, K. R. Wilhelmus; Expression of Vascular Endothelial Growth Factor and Evolution of Corneal Neovascularization During Experimental Candida albicans Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5533.
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To investigate the expression of vascular endothelial growth factor (VEGF) and the progression and inhibition of corneal angiogenesis during experimental keratomycosis.
Scarified corneas of adult BALB/c mice were topically inoculated with Candida albicans strain SC5314 and monitored daily by slit-lamp microscopy over one week for corneal neovascularization. Three groups of pooled infected corneas (5/group) were compared to mock-inoculated controls at 1 day post inoculation (p.i.) with a murine gene microarray. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine levels of VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PGF) for 15 infected and 15 mock-inoculated corneas at 1, 3, and 7 days p.i. and for 15 normal corneas. Immunostaining localized VEGF-A in corneal histologic sections at 1 day p.i. Monoclonal antibody to block the effects of VEGF-A was administered to determine its inhibitory effect on corneal neovascularization.
Eyes inoculated with C. albicans developed limbal capillary budding at day 2 p.i., and corneal blood vessels subsequently grew at the rate of 0.4±0.1 mm/day to reach the central cornea by day 7 p.i. Genes encoding VEGF-A were upregulated 12.5-fold (p<0.001) by microarray and 8.8-fold (p=0.004) by real-time RT-PCR at 1 day p.i, VEGF-A expression then decreased toward baseline over the week following onset. VEGF-B and VEGF-D were initially downregulated 2.9-fold and 3.9-fold, respectively, at day 1 p.i. by real-time RT-PCR but returned to normal levels by day 3 p.i. VEGF-C and PGF showed no significantly different changes between infected and mock control corneas. Scarification of mock corneas did not significantly affect VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF expression compared to the normal cornea. VEGF-A protein was present in the epithelium and stroma of infected corneas. Possible differences of the effect of anti-VEGF-A antibody on corneal neovascularization and fungal keratitis were determined.
Fungal keratitis induces VEGF-A expression and corneal neovascularization. The effect of anti-VEGF-A antibody on corneal neovascularization offers a potential opportunity for therapeutic intervention during keratomycosis.
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