title: Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.
abstract: Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6-24 h resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time-dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions.
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Caiying
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuse
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: eduh@jhmi.edu.
authors.forename: Elia J
authors.initials: EJ
authors.lastname: Duh
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002452:Cell Count; D002460:Cell Line; D005786:Gene Expression Regulation; D008027:Light / Q000009:adverse effects*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D000066829:Neuroprotection; D018384:Oxidative Stress; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012313:RNA / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D012313:RNA
keywords: Neuroprotection; Nrf2; Oxidative stress; Photoreceptor