Abstract
Purpose: :
To evaluate the cytotoxicity of varying doses of Bevacizumab on corneal endothelial cells in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug that neutralizes all isoforms of VEGF, is commonly used as an intracameral agent for the treatment of neovascularization of the iris and the angle. However, the safety of intracameral administration of bevacizumab and dose-dependent toxicity on corneal endothelial cells has not been established.
Methods: :
Bovine corneal endothelial (BCE) cells were treated with VEGF (50 ng/ml) and/or bevacizumab (0.1-2 mg/ml) for 72h. Cytotoxicity in response to bevacizumab was evaluated by trypan blue exclusion, as well as Annexin V / Propidium Iodide (PI) staining. Cell proliferation was measured with the WST-1 assay. Morphological changes were recorded by brightfield microscopy of cells.
Results: :
Bevacizumab was not cytotoxic at the concentrations tested and the percentage of bevacizumab-treated cells staining positively for both PI and Annexin V was less than 1%. The anti-proliferative effects of bevacizumab on BCE cells were dose-dependent; a dose of 1.5 mg/ml or 2 mg/ml produced a 33% (P=0.005) or 47% (P=0.001) decrease in cell proliferation compared to controls. Similar results were obtained in cells treated with a combination of bevacizumab and VEGF. VEGF (50 ng/ml) had no significant effect on cell proliferation compared to controls. Morphology of cells was unchanged after treatment with bevacizumab and/or VEGF compared to controls.
Conclusions: :
Bevacizumab was safe and not toxic to BCE cells at concentrations commonly used in clinical practice as intracameral agent.
Keywords: cornea: endothelium • neovascularization • vascular endothelial growth factor