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M. G. Roberts, R. K. Sharma, C. N. Nagineni, A. Grover, K. V. Chalam; Evaluation of Bevacizumab Cytotoxicity on Human Corneal Cell Lines. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1486.
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Corneal neovascularization occurs in several conditions, including inflammatory, infectious, degenerative, traumatic, and iatrogenic processes. Blood vessels infiltrate the cornea from the limbal vascular plexus. Vascular Endothelial Growth Factor (VEGF) plays an important role in stimulating and maintaining corneal neovascularization. Bevacizumab is a full length recombinant humanized monoclonal antibody that binds to VEGF, and it is being successfully used as anti-VEGF therapy. The promising outlook of this anti-VEGF therapy has prompted the off- label topical use of bevacizumab for corneal neovascularization. Whether such a therapy has any adverse effect on the corneal cells is not well studied. In this study, we investigated the effect bevacizumab on corneal and vascular endothelial cells in culture.
Human corneal epithelial (HCE), human corneal fibroblast (HCRF) cell lines, and human umbilical vein endothelial (HUVEC) cell line, representing cells likely to exposed in topical treatment were used in the study. Cells were exposed to increasing doses (0.1, 1 and 2 mg/ml) of bevacizumab. Cytotoxic and proliferative effects of this treatment were assessed by quantifying the cell numbers by WST-1 and crystal violet staining. Cell death was also assessed by flow cytometry and fluorescent microscopy using propidium iodide staining.
There were no cytotoxic effects of bevacizumab seen in any of the three cell lines (p <0.05). Flow cytometric analysis and fluorescent microscopy supported these results. There was a dose dependant effect on proliferation on all three cell lines. HCRF proliferation increased up to 26% (SE 3.7; p <0.001), HCE up to 24% (SE 4.5; p <0.005) and HUVEC up to 37% (SE 10.6; p <0.01) with 2 mg/ml bevacizumab treatment as assessed with WST-1. Crystal violet assessment showed HCRF proliferation increased up to 35% (SE 2.4; p <0.0001), HCE up to 45% (SE 5.4; p <0 .001) and HUVEC up 8% (SE 2.3; p <0.01) with 2 mg/ml bevacizumab treatment.
Bevacizumab was not cytotoxic to human corneal fibroblast and epithelial cells nor to human umbilical vein endothelial cells. All three cell lines showed evidence of proliferation upon exposure to bevacizumab.
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