RRC ID 56582
Author Chae JB, Rho CR, Shin JA, Lyu J, Kang S.
Title Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells.
Journal Korean J Ophthalmol
Abstract PURPOSE:Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells.
METHODS:Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept.
RESULTS:Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells.
CONCLUSIONS:Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.
Volume 32(4)
Pages 328-338
Published 2018-8-1
DOI 10.3341/kjo.2017.0079
PII 32.328
PMID 30091312
PMC PMC6085187
MeSH Angiogenesis Inhibitors / pharmacology* Bevacizumab / pharmacology* Blotting, Western Cell Survival / drug effects Cells, Cultured Humans In Situ Nick-End Labeling Induced Pluripotent Stem Cells Phagocytosis / drug effects Ranibizumab / pharmacology* Receptors, Vascular Endothelial Growth Factor Recombinant Fusion Proteins / pharmacology* Retinal Pigment Epithelium / drug effects* Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A / antagonists & inhibitors
Resource
Human and Animal Cells hiPSC