Elsevier

Redox Biology

Volume 37, October 2020, 101623
Redox Biology

Research Paper
Oxidative stress in the retina and retinal pigment epithelium (RPE): Role of aging, and DJ-1

https://doi.org/10.1016/j.redox.2020.101623Get rights and content
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Highlights

  • Antioxidants are upregulated in young DJ-1 KO RPE but downregulated in the retina.

  • DJ-1 KO retinas are degenerated under low-level oxidative stress, regardless of age.

  • Retinas of both young C57BL and DJ-1 KO were able to regulate antioxidant genes upon low-level oxidative stress.

  • Retinas of both aged C57BL and DJ-1 KO were unable to regulate antioxidant genes upon low-level oxidative stress.

  • RPE of aged C57BLl mice upregulated some antioxidant genes.

Abstract

High levels of oxidative radicals generated by daily light exposure and high metabolic rate suggest that the antioxidant machinery of the retina and retinal pigment epithelium (RPE) is crucial for their survival. DJ-1 is a redox-sensitive protein that has been shown to have neuroprotective function in the brain in Parkinson's disease and other neurodegenerative diseases. Here, we analyzed the role of DJ-1 in the retina during oxidative stress and aging. We induced low-level oxidative stress in young (3-month-old) and old (15-month-old) C57BL/6J (WT) and DJ-1 knockout (KO) mice and evaluated effects in the RPE and retina. Absence of DJ-1 resulted in increased retinal dysfunction in response to low levels of oxidative stress. Our findings suggest that loss of DJ-1 affects the RPE antioxidant machinery, rendering it unable to combat and neutralize low-level oxidative stress, irrespective of age. Moreover, they draw a parallel to the retinal degeneration observed in AMD, where the occurrence of genetic variants may leave the retina and RPE unable to fight sustained, low-levels of oxidative stress.

Keywords

Retina
Retinal pigment epithelium
Oxidative stress
Aging
DJ-1
Sodium iodate

Abbreviations

AGE
advanced glycation end product
AMD
age-related macular degeneration
BM
Bruch's membrane
CTCF
corrected total cell fluorescence
GFAP
anti-glial fibrillary acidic protein
PD
Parkinson's disease
ROS
reactive oxygen species
RPE
retinal pigment epithelium

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Present address: Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.