Abstract
Purpose: :
VEGF (vascular endothelial growth factor) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence wound healing. Here, we evaluate the effects of bevacizumab on corneal wound healing time in rabbit model, corneal proliferation, and the expression of integrins in human corneal epithelial and fibroblast cells.
Methods: :
To compare corneal healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, or 1.5, 3mg/mL, twice daily, to mechanically debrided epithelium of rabbit cornea. Cellular covering of wounded area was assessed after scrape injury in cultures of human corneal epithelial and fibroblast cells. Expressions of cell surface integrins and collagens were 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 or 1.5 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 and mRNA levels encoding integrins and collagens were decreased by bevacizumab 1.5 mg/mL treatment.
Conclusions: :
Bevacizumab delayed corneal wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, delays in wound healing and cellular proliferation are to be expected.
Keywords: vascular endothelial growth factor • cornea: basic science • wound healing