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Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells
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Type
Academic journal
Author
Journal
대한안과학회 Korean Journal of Ophthalmology Korean Journal of Ophthalmology 제32권 제4호 KCI Accredited Journals
Published
2018.1
Pages
328 - 338 (11page)

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Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells
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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.

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References (31)

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Fine SL / 2000 / Age-related macular degeneration / N Engl J Med 342:483~492 Crossref Kliffen M / 1997 / Increased expression of angiogenic growth factors in age-related maculopathy / Br J Ophthalmol 81:154~162 Crossref Rakic JM / 2003 / Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization / Invest Ophthalmol Vis Sci 44:3186~3193 Crossref Kozlowski MR / 2012 / RPE cell senescence: a key contributor to age-related macular degeneration / Med Hypotheses 78:505~510 Crossref Marazita MC / 2016 / Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: implications for age-related macular degeneration / Redox Biol 7:78~87 Crossref

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