Bevacizumab application delays epithelial healing in rabbit cornea

Tae Im Kim, Jae Lim Chung, Jin Pyo Hong, Kyung Min, Kyoung Yul Seo, Eung Kweon Kim

Research output: Contribution to journalArticle

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Abstract

PURPOSE. Vascular endothelial growth factor (VEGF) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence epithelial wound healing. Here, the effects of bevacizumab on corneal epithelial wound healing time in rabbit models, cell proliferation, and expression of integrins in human corneal epithelial and fibroblast cells were evaluated. METHODS. To compare epithelial wound healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, 1.5, 2.5, or 5 mg/mL, twice daily, to mechanically debrided epithelia of rabbit corneas. The cellular covering of wounded areas and expression of Ki67 were assessed after scrape injuries in cultures of human corneal epithelial and fibroblast cells. Expression of cell surface integrins and collagens was measured using plates coated with mouse monoclonal antibodies against human adhesion molecules, and relevant mRNA levels were assessed by reversetranscription-polymerase chain reaction (RT-PCR). RESULTS. The application of bevacizumab topical eye drops at 1.0, 1.5, 2.5, or 5 mg/mL delayed rabbit corneal epithelial healing. Cell cultures growing under high concentrations of bevacizumab showed delay in the proliferation of corneal epithelial and fibroblast cells. Surface expression of mRNA encoding integrins and collagens were decreased by 1.5 mg/mL of bevacizumab. CONCLUSIONS. Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.

Original languageEnglish
Pages (from-to)4653-4659
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number10
DOIs
Publication statusPublished - 2009 Dec 1

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Cornea
Rabbits
Wound Healing
Integrins
Fibroblasts
Ophthalmic Solutions
Epithelial Cells
Vascular Endothelial Growth Factor A
Collagen
Cell Proliferation
Messenger RNA
Bevacizumab
Epithelium
Cell Culture Techniques
Monoclonal Antibodies
Polymerase Chain Reaction
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

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title = "Bevacizumab application delays epithelial healing in rabbit cornea",
abstract = "PURPOSE. Vascular endothelial growth factor (VEGF) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence epithelial wound healing. Here, the effects of bevacizumab on corneal epithelial wound healing time in rabbit models, cell proliferation, and expression of integrins in human corneal epithelial and fibroblast cells were evaluated. METHODS. To compare epithelial wound healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, 1.5, 2.5, or 5 mg/mL, twice daily, to mechanically debrided epithelia of rabbit corneas. The cellular covering of wounded areas and expression of Ki67 were assessed after scrape injuries in cultures of human corneal epithelial and fibroblast cells. Expression of cell surface integrins and collagens was measured using plates coated with mouse monoclonal antibodies against human adhesion molecules, and relevant mRNA levels were assessed by reversetranscription-polymerase chain reaction (RT-PCR). RESULTS. The application of bevacizumab topical eye drops at 1.0, 1.5, 2.5, or 5 mg/mL delayed rabbit corneal epithelial healing. Cell cultures growing under high concentrations of bevacizumab showed delay in the proliferation of corneal epithelial and fibroblast cells. Surface expression of mRNA encoding integrins and collagens were decreased by 1.5 mg/mL of bevacizumab. CONCLUSIONS. Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.",
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Bevacizumab application delays epithelial healing in rabbit cornea. / Kim, Tae Im; Chung, Jae Lim; Hong, Jin Pyo; Min, Kyung; Seo, Kyoung Yul; Kim, Eung Kweon.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 10, 01.12.2009, p. 4653-4659.

Research output: Contribution to journalArticle

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T1 - Bevacizumab application delays epithelial healing in rabbit cornea

AU - Kim, Tae Im

AU - Chung, Jae Lim

AU - Hong, Jin Pyo

AU - Min, Kyung

AU - Seo, Kyoung Yul

AU - Kim, Eung Kweon

PY - 2009/12/1

Y1 - 2009/12/1

N2 - PURPOSE. Vascular endothelial growth factor (VEGF) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence epithelial wound healing. Here, the effects of bevacizumab on corneal epithelial wound healing time in rabbit models, cell proliferation, and expression of integrins in human corneal epithelial and fibroblast cells were evaluated. METHODS. To compare epithelial wound healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, 1.5, 2.5, or 5 mg/mL, twice daily, to mechanically debrided epithelia of rabbit corneas. The cellular covering of wounded areas and expression of Ki67 were assessed after scrape injuries in cultures of human corneal epithelial and fibroblast cells. Expression of cell surface integrins and collagens was measured using plates coated with mouse monoclonal antibodies against human adhesion molecules, and relevant mRNA levels were assessed by reversetranscription-polymerase chain reaction (RT-PCR). RESULTS. The application of bevacizumab topical eye drops at 1.0, 1.5, 2.5, or 5 mg/mL delayed rabbit corneal epithelial healing. Cell cultures growing under high concentrations of bevacizumab showed delay in the proliferation of corneal epithelial and fibroblast cells. Surface expression of mRNA encoding integrins and collagens were decreased by 1.5 mg/mL of bevacizumab. CONCLUSIONS. Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.

AB - PURPOSE. Vascular endothelial growth factor (VEGF) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence epithelial wound healing. Here, the effects of bevacizumab on corneal epithelial wound healing time in rabbit models, cell proliferation, and expression of integrins in human corneal epithelial and fibroblast cells were evaluated. METHODS. To compare epithelial wound healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, 1.5, 2.5, or 5 mg/mL, twice daily, to mechanically debrided epithelia of rabbit corneas. The cellular covering of wounded areas and expression of Ki67 were assessed after scrape injuries in cultures of human corneal epithelial and fibroblast cells. Expression of cell surface integrins and collagens was measured using plates coated with mouse monoclonal antibodies against human adhesion molecules, and relevant mRNA levels were assessed by reversetranscription-polymerase chain reaction (RT-PCR). RESULTS. The application of bevacizumab topical eye drops at 1.0, 1.5, 2.5, or 5 mg/mL delayed rabbit corneal epithelial healing. Cell cultures growing under high concentrations of bevacizumab showed delay in the proliferation of corneal epithelial and fibroblast cells. Surface expression of mRNA encoding integrins and collagens were decreased by 1.5 mg/mL of bevacizumab. CONCLUSIONS. Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.

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