Idebenone Prevents Retinal Pigmentepithelium (RPE) Cells from Oxidative Stress and Senescence

Abstract

Purpose: : Age related macular degeneration (AMD) is one of the leading causes of blindness. Oxidative stress plays an important role in the pathogenesis of this disease. This study investigates the potential anti-apoptotic and cytoprotective effects of idebenone on retinal pigment epithelial cells (ARPE19) under oxidative stress.

Methods: : ARPE19 were treated with 1 to 100 µM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species (ROS) and senescence-associated β-galactosidase (SA β-Gal) activity were investigated. In addition, expression of BAX and Bcl-2, and their mRNA were determined after 48 h and after H₂O₂ treatment.

Results: : Idebenone concentrations from 1 to 20 µM showed no toxic effects on ARPE19. Pretreatment with 5 and 7.5 µM idebenone led to an increase in viability of ARPE19 after H₂O₂ treatment. In addition, idebenone pretreatment significantly attenuated the induction of SA β-Gal and intracellular ROS after treatment with H₂O₂. When ARPE19 were treated with idebenone and H₂O₂, rt-PCR and Western blot analysis yielded a trend towards, but no significant increase in expression of Bcl-2 and decrease of BAX, compared to those cells that were treated with H₂O₂ only.

Conclusions: : In this study idebenone increased survival of ARPE19 cells and reduced senescence and oxidative stress. Our results suggest that idebenone may help to protect the RPE against oxidative stress. However, these effects may be modulated by of other pathways than the Bcl-2/BAX pathway.

Keywords: retinal pigment epithelium • oxidation/oxidative or free radical damage • age-related macular degeneration