中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (10): 2173-2181.doi: 10.4103/1673-5374.369098

• 综述:视神经损伤修复保护与再生 • 上一篇    下一篇

美国哈佛医学院Jing Chen团队总结氧化应激在视网膜色素上皮变性中的作用

  

  • 出版日期:2023-10-15 发布日期:2023-03-28

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

Meenakshi Maurya, Kiran Bora, Alexandra K. Blomfield, Madeline C. Pavlovich, Shuo Huang, Chi-Hsiu Liu, Jing Chen*   

  1. Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
  • Online:2023-10-15 Published:2023-03-28
  • Contact: Jing Chen, PhD, Jing.Chen@childrens.harvard.edu.
  • Supported by:
    This work was supported by NIH/NEI R01 grants (EY031765, EY028100, and EY024963), BrightFocus Foundation, Research to Prevent Blindness Dolly Green Special Scholar Award, Boston Children’s Hospital Ophthalmology Foundation, and Mass Lions Eye Research Fund Inc. (to JC).

摘要: https://orcid.org/0000-0002-9183-8698 (Jing Chen)

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.

Key words: age-related macular degeneration, antioxidant, nuclear factor erythroid-2-related factor 2, oxidative stress, retinal pigment epithelium, REV-ERBα