Puddu Alessandra, Sanguineti Roberta, Traverso Carlo Enrico, Viviani Giorgio L, Nicolò Massimo
Department of Internal Medicine and Medical Specialties, Genova - Italy.
Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy.
Eur J Ophthalmol. 2016 Aug 4;26(5):425-30. doi: 10.5301/ejo.5000786. Epub 2016 Apr 12.
The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro.
ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs.
Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.
年龄相关性黄斑变性的新生血管或湿性形式的特征是视网膜中异常血管的生长，这是由血管内皮生长因子（VEGF）刺激引起的。在过去十年中，已经开发了几种抗VEGF药物用于治疗眼部新生血管疾病。本研究旨在比较两种抗VEGF-A药物雷珠单抗和阿柏西普对视网膜色素上皮细胞（RPE）中VEGF家族成员表达和分泌的体外影响。
将ARPE-19细胞暴露于临床剂量浓度的雷珠单抗或阿柏西普24小时。分别通过实时聚合酶链反应和酶联免疫吸附测定评估细胞活力以及VEGF-A、VEGF-B、VEGF-C和胎盘生长因子（PlGF）的表达和分泌。
治疗24小时后，雷珠单抗和阿柏西普不影响ARPE-19细胞活力。雷珠单抗增加VEGF-A和PlGF的表达。相反，雷珠单抗降低VEGF-C的表达和分泌。雷珠单抗不影响PlGF的分泌。阿柏西普强烈增加VEGF-A和PlGF的表达，但降低其在培养基中的检测量，并降低VEGF-C的表达和分泌。暴露于这些药物后，未观察到对VEGF-B表达和分泌的影响。
雷珠单抗和阿柏西普对VEGF表达和分泌具有相似作用，从而建立抗血管生成环境。在用这些药物处理的RPE细胞中观察到的VEGF-A表达增加表明细胞对VEGF-A缺乏的代偿反应。
