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Corneal neovascularization during experimental fungal keratitis

PURPOSE: To investigate the development of corneal neovascularization, the corneal expression of vascular endothelial growth factor (VEGF), and the antiangiogenic effects of a VEGF-inhibitory antibody during experimental keratomycosis. METHODS: Scarified corneas of BALB/c mice were topically inocula...

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Autores principales: Yuan, Xiaoyong, Wilhelmus, Kirk R.
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756518/
https://www.ncbi.nlm.nih.gov/pubmed/19816603
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author Yuan, Xiaoyong
Wilhelmus, Kirk R.
author_facet Yuan, Xiaoyong
Wilhelmus, Kirk R.
author_sort Yuan, Xiaoyong
collection PubMed
description PURPOSE: To investigate the development of corneal neovascularization, the corneal expression of vascular endothelial growth factor (VEGF), and the antiangiogenic effects of a VEGF-inhibitory antibody during experimental keratomycosis. METHODS: Scarified corneas of BALB/c mice were topically inoculated with Candida albicans and monitored daily for corneal neovascularization. A murine gene microarray compared infected corneas to controls 1 day after inoculation. 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 corneal sections. An anti-VEGF-A antibody that binds to murine VEGF was evaluated for effects on corneal neovascularization and fungal recovery. RESULTS: Eyes with C. albicans keratitis manifested limbal capillary budding on the second postinoculation day, and intrastromal neovascular tufts subsequently grew 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-A was present in the epithelium and stroma of infected corneas. Scarification alone did not alter VEGF expression compared to the normal cornea. Anti-VEGF-A antibody significantly (p<0.01) decreased the formation of new corneal blood vessels during experimental keratomycosis without adversely affecting the fungal load of C. albicans keratitis. CONCLUSIONS: Untreated C. albicans keratitis induces VEGF-A and leads to progressive corneal neovascularization that is preventable by a VEGF-blocking antibody.
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spelling pubmed-27565182009-10-08 Corneal neovascularization during experimental fungal keratitis Yuan, Xiaoyong Wilhelmus, Kirk R. Mol Vis Research Article PURPOSE: To investigate the development of corneal neovascularization, the corneal expression of vascular endothelial growth factor (VEGF), and the antiangiogenic effects of a VEGF-inhibitory antibody during experimental keratomycosis. METHODS: Scarified corneas of BALB/c mice were topically inoculated with Candida albicans and monitored daily for corneal neovascularization. A murine gene microarray compared infected corneas to controls 1 day after inoculation. 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 corneal sections. An anti-VEGF-A antibody that binds to murine VEGF was evaluated for effects on corneal neovascularization and fungal recovery. RESULTS: Eyes with C. albicans keratitis manifested limbal capillary budding on the second postinoculation day, and intrastromal neovascular tufts subsequently grew 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-A was present in the epithelium and stroma of infected corneas. Scarification alone did not alter VEGF expression compared to the normal cornea. Anti-VEGF-A antibody significantly (p<0.01) decreased the formation of new corneal blood vessels during experimental keratomycosis without adversely affecting the fungal load of C. albicans keratitis. CONCLUSIONS: Untreated C. albicans keratitis induces VEGF-A and leads to progressive corneal neovascularization that is preventable by a VEGF-blocking antibody. Molecular Vision 2009-09-29 /pmc/articles/PMC2756518/ /pubmed/19816603 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yuan, Xiaoyong
Wilhelmus, Kirk R.
Corneal neovascularization during experimental fungal keratitis
title Corneal neovascularization during experimental fungal keratitis
title_full Corneal neovascularization during experimental fungal keratitis
title_fullStr Corneal neovascularization during experimental fungal keratitis
title_full_unstemmed Corneal neovascularization during experimental fungal keratitis
title_short Corneal neovascularization during experimental fungal keratitis
title_sort corneal neovascularization during experimental fungal keratitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756518/
https://www.ncbi.nlm.nih.gov/pubmed/19816603
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