Evaluation of cytotoxicity of bevacizumab on VEGF-enriched corneal endothelial cells.

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 widely used in the treatment of neovascular glaucoma neutralizes all isoforms of VEGF and ameliorates neovascularization after intracameral administration. 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 72 h. Cell proliferation was measured with the water soluble tetrazolium salts (WST-1) assay. Morphological changes were recorded by bright-field microscopy of cells. Cytotoxicity in response to Bevacizumab was evaluated by trypan blue exclusion, as well as annexin V/propidium iodide (PI) staining.

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.

• Authors: Raluca Rusovici, Monali Sakhalkar, Kakarla V Chalam
• Journal: Molecular vision (Mol Vis) Vol. 17 Pg. 3339-46 ( 2011) ISSN: 1090-0535 [Electronic] United States
• PMID: 22219629 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Annexin A5
• Antibodies, Monoclonal, Humanized
• Vascular Endothelial Growth Factor A
• Bevacizumab
• Trypan Blue

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Annexin A5
• Anterior Chamber (blood supply)
• Antibodies, Monoclonal, Humanized (pharmacology)
• Bevacizumab
• Cattle
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cornea (drug effects, metabolism, pathology)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism, pathology)
• Glaucoma, Neovascular (drug therapy, pathology)
• Humans
• Microscopy
• Neovascularization, Pathologic
• Trypan Blue
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, pharmacology)