Schicht M, Hesse K, Schröder H, Naschberger E, Lamprecht W, Garreis F, Paulsen F P, Bräuer L
Institute of Anatomy, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Institute of Anatomy, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Ann Anat. 2017 May;211:135-139. doi: 10.1016/j.aanat.2017.02.005. Epub 2017 Mar 7.
Pathological formation of blood vessels plays a key role in the growth and metastasis of tumors and also in several serious ophthalmological diseases such as wet age-related macular degeneration (AMD) or diabetic retinopathy. In AMD treatment, aflibercept (tradename EYLEA) is used to deactivate the underlying pathological neovascularisation. Aflibercept is a recombinant fusion protein which binds to vascular endothelial growth factor (VEGF) receptors, thereby inhibiting VEGF pathway activation. VEGF is one of the most important angiogenesis factors.
This analysis investigates lasting efficacy of aflibercept in vitro for later application as therapeutic agent against macular degeneration (AMD).
VEGF-ELISA assays were performed to investigate binding affinities at different aflibercept concentrations. The impact of VEGF on the proliferation of human umbilical vein endothelial cells (HUVEC) was investigated using proliferation assays. Moreover, time-dependent kinetic studies were performed to analyze different aflibercept storage durations with regard to its inhibitory capabilities on human VEGF.
Our results reveal that aflibercept significantly lowers the amount of unbound VEGF as well as the proliferation rate of HUVEC. Moreover, in contrast to specifications given by the manufacturer, aflibercept retains its full inhibitory effect up to at least 120h after transference from the original vial into the injection syringe.
血管的病理性形成在肿瘤的生长和转移以及几种严重的眼科疾病（如湿性年龄相关性黄斑变性（AMD）或糖尿病性视网膜病变）中起着关键作用。在AMD治疗中，阿柏西普（商品名EYLEA）用于使潜在的病理性新生血管化失活。阿柏西普是一种重组融合蛋白，它与血管内皮生长因子（VEGF）受体结合，从而抑制VEGF信号通路的激活。VEGF是最重要的血管生成因子之一。
本分析研究阿柏西普在体外的持久疗效，以便日后作为治疗黄斑变性（AMD）的药物应用。
进行VEGF-ELISA检测以研究不同阿柏西普浓度下的结合亲和力。使用增殖检测方法研究VEGF对人脐静脉内皮细胞（HUVEC）增殖的影响。此外，进行了时间依赖性动力学研究，以分析不同阿柏西普储存时间对其抑制人VEGF能力的影响。
我们的结果表明，阿柏西普显著降低了未结合VEGF的量以及HUVEC的增殖率。此外，与制造商给出的规格相反，阿柏西普从原始药瓶转移到注射器后，至少在120小时内仍保持其完全抑制作用。
