Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosensory retinal, and microvascular endothelial cells.
OBJECTIVE
To evaluate the short-term in vitro safety of bevacizumab (Avastin) in human retinal pigment epithelial (ARPE-19), rat neurosensory retinal (R28), and human microvascular endothelial (HMVECad) cells.


METHODS
ARPE-19 and R28 cells were treated with 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of bevacizumab for 2, 6, and 24 hours. HMVECad cells were treated with 5 ng/mL of vascular endothelial growth factor (VEGF) and 0.125 mg/mL, 0.25 mg/mL, 0.50 mg/mL, and 1 mg/mL of either bevacizumab for 2, 6, and 24 hours or a nonspecific human purified immunoglobulin (IgG) for 24 hours. Cell viability was measured using trypan blue dye exclusion assay.


RESULTS
The cell viabilities of ARPE-19 cells, R28 cells, and HMVECad cells treated with bevacizumab were not significantly different (P > 0.05) from that of untreated controls. There was no significant difference (P > 0.05) between viabilities of HMVECad cells treated with bevacizumab and IgG.


CONCLUSIONS
This study suggests that bevacizumab, at concentrations at or above the dose normally used in clinical practice, is not toxic to human retinal pigment epithelial, rat neurosensory retinal, or human microvascular endothelial cells in vitro. This report is consistent with the recent report of lack of toxicity of intravitreal bevacizumab in rabbits as well as the lack of apparent toxicity in clinical use.
Luthra
Saurabh
S
Department of Ophthalmology, University of California, Irvine, 92697, USA.
Narayanan
Raja
R
Marques
L Eduardo A
LE
Chwa
Marilyn
M
Kim
Dae W
DW
Dong
Joyce
J
Seigel
Gail M
GM
Neekhra
Aneesh
A
Gramajo
Ana L
AL
Brown
Donald J
DJ
Kenney
M Cristina
MC
Kuppermann
Baruch D
BD
D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018929:Cell Culture Techniques; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000187:drug effects*; D012160:Retina / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab