Effects of commonly used intravitreal anti-vascular endothelial growth factor drugs on mesenchymal stem cells derived from the limbus and ciliary body.

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 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.

Conclusion: 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.