Acar Ugur, Erginturk Acar Damla, Alpaslan Pinarli Ferda, Demir Muhammed N, Beyazyildiz Emrullah, Ozdemir Ozdemir, Gulmez Sevim Duygu, Tiryaki Meral, Sobaci Gungor
Department of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
Department of Ophthalmology, Ministry of Health, Zekai Tahir Burak Women's Health Training and Research Hospital, Ankara, Turkey.
Clin Exp Ophthalmol. 2016 Sep;44(7):587-596. doi: 10.1111/ceo.12715. Epub 2016 Mar 19.
To investigate the effects of commonly used intravitreal anti-vascular endothelial growth factor (anti-VEGF) antibodies on proliferation index and viability of mesenchymal stem cells derived from ciliary body and limbus (CB-MSC and LMSC).
CB-MSCs and LMSCs were isolated from newborn rats' eyes, and they were expanded in medium by the explant method. Intravitreally used anti-VEGF drugs, aflibercept, bevacizumab and ranibizumab were tested into the 16-well plates, respectively, at four different concentrations. After keeping them for 48 h, the proliferation indexes and viabilities of CB-MSCs and LMSCs were compared separately by Real-Time Cell Analyzer and Methylthiazoltetrazoli (MTT) test.
Anti-VEGFs used at 5-times and 10-times of the standard clinical dosage caused statistically significant negative effects on proliferation indexes of CB-MSCs and LMSCs at the 24 hour compared to control group. Only the anti-VEGF group that had 10-times dosage of those used clinically had a statistically significant negative effect on the viabilties of CB-MSCs and LMSCs.
Administrations of high doses or repeated standard doses of intravitreal anti-VEGF agents may affect the proliferation indexes and viabilities of CB-MSCs and LMSCs adversely. These novel findings deserve further in vivo investigations.
探讨常用玻璃体内抗血管内皮生长因子(抗VEGF)抗体对睫状体和角膜缘间充质干细胞(CB-MSC和LMSC)增殖指数和活力的影响。
从新生大鼠眼中分离出CB-MSCs和LMSCs,采用组织块培养法在培养基中进行扩增。将玻璃体内使用的抗VEGF药物阿柏西普、贝伐单抗和雷珠单抗分别以四种不同浓度加入16孔板中。作用48小时后,分别通过实时细胞分析仪和甲基噻唑基四氮唑(MTT)试验比较CB-MSCs和LMSCs的增殖指数和活力。
与对照组相比,标准临床剂量5倍和10倍的抗VEGF药物在24小时时对CB-MSCs和LMSCs的增殖指数产生了具有统计学意义的负面影响。只有临床使用剂量10倍的抗VEGF组对CB-MSCs和LMSCs的活力产生了具有统计学意义的负面影响。
玻璃体内高剂量或重复标准剂量使用抗VEGF药物可能会对CB-MSCs和LMSCs的增殖指数和活力产生不利影响。这些新发现值得进一步进行体内研究。