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Cited by 63Retinal Diseases and TreatmentsRetinal Development and DisordersRetinal Imaging and Analysis

Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration

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Maurya, Meenakshi, Bora, Kiran, Blomfield, Alexandra K., Pavlovich, Madeline C., Huang, Shuo, Liu, Chi-Hsiu, Chen, Jing·2023·Neural Regeneration Research
DOI 10.4103/1673-5374.369098PMC PMC10328284
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Abstract

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

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Authors
Maurya, M., Bora, K., Blomfield, A. K., Pavlovich, M. C., Huang, S., Liu, C.-H., & Chen, J.
Affiliations
Boston Children's Hospital (US)
Corresponding author
Chen, Jing
ORCID
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2023-03-03
Volume
18
Issue
10
Pages
2173-2181
ISSN
  • 1673-5374 (ISSN-L)
  • 1876-7958
DOI
10.4103/1673-5374.369098
PMC
PMC10328284
OpenAlex
W4320923661
Cited by
63
References
197
Citations by year
2026: 27 · 2025: 14 · 2024: 14 · 2023: 8
FWCI
3.21
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Research to Prevent Blindness
  • BrightFocus Foundation
  • National Institutes of Health
  • National Eye Institute (EY024963, EY031765, R01EY028100, R01EY031765, R01EY024963)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords
oxidative stress, retinal pigment epithelium degeneration, dry age-related macular degeneration, Nrf2, NR1D1, antioxidant enzymes, disease progression, therapeutic target

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