Luthra Saurabh, Narayanan Raja, Marques L Eduardo A, Chwa Marilyn, Kim Dae W, Dong Joyce, Seigel Gail M, Neekhra Aneesh, Gramajo Ana L, Brown Donald J, Kenney M Cristina, Kuppermann Baruch D
Department of Ophthalmology, University of California, Irvine, 92697, USA.
Retina. 2006 May-Jun;26(5):512-8. doi: 10.1097/01.iae.0000222547.35820.52.
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.
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.
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.
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.
评估贝伐单抗(阿瓦斯汀)在人视网膜色素上皮(ARPE - 19)细胞、大鼠神经感觉视网膜(R28)细胞和人微血管内皮(HMVECad)细胞中的短期体外安全性。
用0.125mg/mL、0.25mg/mL、0.50mg/mL和1mg/mL的贝伐单抗处理ARPE - 19细胞和R28细胞2小时、6小时和24小时。用5ng/mL的血管内皮生长因子(VEGF)以及0.125mg/mL、0.25mg/mL、0.50mg/mL和1mg/mL的贝伐单抗处理HMVECad细胞2小时、6小时和24小时,或用非特异性人纯化免疫球蛋白(IgG)处理24小时。使用台盼蓝染料排除法测量细胞活力。
用贝伐单抗处理的ARPE - 19细胞、R28细胞和HMVECad细胞的细胞活力与未处理的对照相比无显著差异(P>0.05)。用贝伐单抗和IgG处理的HMVECad细胞活力之间无显著差异(P>0.05)。
本研究表明,在临床实践中常用剂量或以上浓度的贝伐单抗在体外对人视网膜色素上皮细胞、大鼠神经感觉视网膜细胞或人微血管内皮细胞无毒。本报告与最近关于玻璃体内注射贝伐单抗对兔无毒性以及临床使用中无明显毒性的报告一致。