title: Effects of commonly used intravitreal anti-vascular endothelial growth factor drugs on mesenchymal stem cells derived from the limbus and ciliary body.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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 24thhour 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey. druguracar@gmail.com.
authors: Ugur
authors: http://orcid.org/0000-0003-2950-8361
authors: U
authors: Acar
authors: Department of Ophthalmology, Ministry of Health, Zekai Tahir Burak Women's Health Training and Research Hospital, Ankara, Turkey.
authors: Damla
authors: D
authors: Erginturk Acar
authors: Cell Research and Genetic Diagnosis Center, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey.
authors: Ferda
authors: F
authors: Alpaslan Pinarli
authors: Department of Ophthalmology, Yıldırım Beyazıt University, Faculty of Medicine, Ankara, Turkey.
authors: Muhammed N
authors: MN
authors: Demir
authors: Department of Ophthalmology, Samsun Training and Research Hospital, Samsun, Turkey.
authors: Emrullah
authors: E
authors: Beyazyildiz
authors: Department of Ophthalmology, Ministry of Health, Zekai Tahir Burak Women's Health Training and Research Hospital, Ankara, Turkey.
authors: Ozdemir
authors: O
authors: Ozdemir
authors: Department of Ophthalmology, Erciyes University, Faculty of Medicine, Kayseri, Turkey.
authors: Duygu
authors: D
authors: Gulmez Sevim
authors: Cell Research and Genetic Diagnosis Center, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey.
authors: Meral
authors: M
authors: Tiryaki
authors: Department of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
authors: Gungor
authors: G
authors: Sobaci
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000068258:Bevacizumab / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002924:Ciliary Body / Q000166:cytology*; D005434:Flow Cytometry; D058449:Intravitreal Injections; D016850:Limbus Corneae / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D000069579:Ranibizumab / Q000494:pharmacology; D051381:Rats; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Aflibercept; anti-VEGF; bevacizumab; ciliary body; intravitreal injection; limbus; mesencyhmal stem cell; ranibizumab