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Arend, Nicole; Wertheimer, Christian; Laubichler, Peter; Wolf, Armin; Kampik, Anselm; Kernt, Marcus (2015): Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio. In: Ophthalmologica, Vol. 234, No. 2: pp. 73-82
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Abstract

PURPOSE Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. METHODS ARPE-19 cells were treated with 1-100 µ\textlesssmlcap\textgreaterM\textless/smlcap\textgreater idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated \textgreekb-galactosidase (SA-\textgreekb-Gal) activity were investigated under exposure to hydrogen peroxide (H2O2). RESULTS Idebenone concentrations from 1 to 20 µ\textlesssmlcap\textgreaterM\textless/smlcap\textgreater showed no toxic effects on ARPE-19 cells. When cells were treated with H2O2, pretreatment with 5, 7.5, 10, and 20 µ\textlesssmlcap\textgreaterM\textless/smlcap\textgreater idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-\textgreekb-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H2O2. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H2O2-induced apoptosis, not necrosis. CONCLUSION In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.