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Shwu-Jiuan Sheu, Ni-Chun Liu, Julie Y.H. Chan; The effects of anti-vascular endothelial growth factor on cell viability, oxidative stress and mitochondrial bioenergetics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6326.
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Age-related macular degeneration (AMD) is one of the major causes of adult visual loss. The vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of neovascular AMD. Anti-VEGF agents have been emerged as potential therapeutics for the treatment of AMD. The long-term effect of the anti-VEGF agent is desirable; however, possible short-term or long-term toxicity is not fully understood. The purpose of this study was to test the effects of two anti-VEGF agents on the cell viability and mitochondrial bioenergetics in human retinal pigment epithelial (RPE) cells.
Cell viability was tested in cultured APRE-19 cells treated with aflibercept (0.125, 0.5, or 2 mg) or ranibizumab (0.125, 0.25, or 0.5 mg) for 72 hours alone or pretreated the agents for 24 hours followed by acrolein (25 μM). Mitochondrial biogenesis was evaluated by Seahorse XF24 Extracellular Flux Analyzer at different time points after exposure to aflibercept or ranibizumab.
After 72-h exposure, both aflibercep and ranibizumab caused mild reduction in cell viability; however, pretreatment with these two agents rescued the oxidative damage induced by acrolein on APRE-19 cells. Both aflibercep and ranibizumab increased basal and maximal mitochondrial respiratory capacity after short-term exposure (1 or 24 h), but returned to baseline following a long-time exposure (48 or 72 h).
Our results suggest that aflibercep and ranibizumab might exert protection against acrolein-induced oxidative cytotoxicity in human ARPE-19 cells via increases in the mitochondrial bioenergetics. Early alteration in mitochondrial reserve capacity might predict possible anti-oxidative effects of the agents.
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