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Originally published In Press as doi:10.1167/iovs.08-2805 on May 20, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:4653-4659.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2805
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Bevacizumab Application Delays Epithelial Healing in Rabbit Cornea

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

From the Corneal Dystrophy Research Institute, Department of Ophthalmology, Yonsei University, College of Medicine, Seoul, Korea.

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 reverse-transcription–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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Copyright © 2009 by the Association for Research in Vision and Ophthalmology