Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light

Wan Ju Chen, Caiying Wu, Zhenhua Xu, Yoshiki Kuse, Hideaki Hara, Elia J Duh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalExperimental Eye Research
Volume154
DOIs
StatePublished - Jan 1 2017

Fingerprint

Photoreceptor Cells
Oxidative Stress
Light
Reactive Oxygen Species
Cell Death
Retinal Degeneration
Macular Degeneration
Drug Delivery Systems
Small Interfering RNA
Genes
Reverse Transcription
Rodentia
Antioxidants
Polymerase Chain Reaction
Wounds and Injuries

Keywords

  • Neuroprotection
  • Nrf2
  • Oxidative stress
  • Photoreceptor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light. / Chen, Wan Ju; Wu, Caiying; Xu, Zhenhua; Kuse, Yoshiki; Hara, Hideaki; Duh, Elia J.

In: Experimental Eye Research, Vol. 154, 01.01.2017, p. 151-158.

Research output: Contribution to journalArticle

Chen, Wan Ju ; Wu, Caiying ; Xu, Zhenhua ; Kuse, Yoshiki ; Hara, Hideaki ; Duh, Elia J. / Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light. In: Experimental Eye Research. 2017 ; Vol. 154. pp. 151-158.
@article{261b47148e014195a9e0718177aa29cd,
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.",
keywords = "Neuroprotection, Nrf2, Oxidative stress, Photoreceptor",
author = "Chen, {Wan Ju} and Caiying Wu and Zhenhua Xu and Yoshiki Kuse and Hideaki Hara and Duh, {Elia J}",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.exer.2016.12.001",
language = "English (US)",
volume = "154",
pages = "151--158",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light

AU - Chen, Wan Ju

AU - Wu, Caiying

AU - Xu, Zhenhua

AU - Kuse, Yoshiki

AU - Hara, Hideaki

AU - Duh, Elia J

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Neuroprotection

KW - Nrf2

KW - Oxidative stress

KW - Photoreceptor

UR - http://www.scopus.com/inward/record.url?scp=85010205127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010205127&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2016.12.001

DO - 10.1016/j.exer.2016.12.001

M3 - Article

C2 - 27923559

AN - SCOPUS:85010205127

VL - 154

SP - 151

EP - 158

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

ER -