Evaluation of differential toxicity of varying doses of bevacizumab on retinal ganglion cells, retinal pigment epithelial cells, and vascular endothelial growth factor-enriched choroidal endothelial cells.
OBJECTIVE
To evaluate in vitro the effects of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, on retinal pigment epithelial cells (RPE) and retinal ganglion cells (RGC), at doses that were inhibitory to VEGF-enriched choroidal endothelial cells (CEC).


METHODS
Monkey CEC (RF6A), human RPE cells (ARPE-19), and rat RGC (RGC-5) were exposed for 24 h to increasing doses of bevacizumab. Cell numbers were quantified with WST-1 assay. Cell death was assessed using propidium iodide (PI) staining via flow cytometry and fluorescent microscopy.


RESULTS
Bevacizumab was inhibitory to RF6A at 2.0 mg/mL (P < 0.005). No effect on cell viability was noted on ARPE-19 and RGC-5 cell lines at this particular dose of bevacizumab. These results were supported by fluorescent microscopy of PI-stained cells.


CONCLUSIONS
VEGF-stimulated proliferation of CEC was inhibited by bevacizumab. Bevacizumab was not cytotoxic to human RPE and rat RGC in vitro at a dose that is inhibitory to monkey CEC.
Brar
Vikram S
VS
Department of Ophthalmology, University of Florida-Jacksonville, Jacksonville, Florida 32209, USA.
Sharma
Rajesh K
RK
Murthy
Ravi K
RK
Chalam
Kakarla V
KV
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D000882:Haplorhini; D006801:Humans; D008856:Microscopy, Fluorescence; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab