评估不同剂量贝伐单抗对视网膜神经节细胞、视网膜色素上皮细胞和富含血管内皮生长因子的脉络膜内皮细胞的差异毒性。
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.
机构信息
Department of Ophthalmology, University of Florida-Jacksonville, Jacksonville, Florida 32209, USA.
出版信息
J Ocul Pharmacol Ther. 2009 Dec;25(6):507-11. doi: 10.1089/jop.2009.0028.
PURPOSE
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.
目的
评估血管内皮生长因子（VEGF）抗体贝伐单抗在体外对视网膜色素上皮细胞（RPE）和视网膜神经节细胞（RGC）的作用，所用剂量对富含 VEGF 的脉络膜内皮细胞（CEC）具有抑制作用。
方法
将猴 CEC（RF6A）、人 RPE 细胞（ARPE-19）和大鼠 RGC（RGC-5）分别用不同浓度的贝伐单抗孵育 24 小时。通过 WST-1 测定法对细胞数量进行定量。通过流式细胞术和荧光显微镜使用碘化丙啶（PI）染色评估细胞死亡。
结果
贝伐单抗在 2.0 mg/mL 时对 RF6A 具有抑制作用（P < 0.005）。在这个特定的贝伐单抗剂量下，对 ARPE-19 和 RGC-5 细胞系没有观察到细胞活力的影响。PI 染色荧光显微镜的结果支持了这一结论。
结论
贝伐单抗抑制了 VEGF 刺激的 CEC 增殖。在抑制猴 CEC 的剂量下，贝伐单抗对体外培养的人 RPE 和大鼠 RGC 没有细胞毒性。
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