The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration
Abstract
Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.
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Compromised energy and protein metabolism in aging retinal photoreceptors and RPE likely constitute one of the early steps in AMD pathogenesis.
“Based on extensive biochemical, pathobiological, and genetic studies implicating oxidative stress and inflammation (12, 64, 165, 174), compromised energy and protein metabolism in aging retinal photoreceptors and RPE likely constitute one of the early steps in AMD pathogenesis (Figure 6).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [12]
Mitochondrial dysfunction and oxidative stress, including mitochondrial DNA damage, have been implicated in AD, PD, and AMD.
“Mitochondrial dysfunction and oxidative stress, including mitochondrial DNA damage, have been implicated in all three diseases—AD, PD, and AMD (12, 17, 98, 165).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [12]
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- Authors
- Beatty, S., Koh, H.-H., Phil, M., Henson, D., & Boulton, M.
- Affiliations
- Manchester Royal Eye Hospital (GB)
- University of Manchester (GB)
- Cardiff University (GB)
- Venue
- Survey of Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 45
- Issue
- 2
- Pages
- 115-134
- ISSN
- 0039-6257 (ISSN-L)
- OpenAlex
- W2144839999
- Cited by
- 2,051
- References
- 243
- Citations by year
- 2026: 51 · 2025: 52 · 2024: 65 · 2023: 80 · 2022: 79 · 2021: 109 · 2020: 68 · 2019: 106 · 2018: 86 · 2017: 92 · 2016: 83 · 2015: 87 · 2014: 104 · 2013: 104 · 2012: 119
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Survey of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, oxidative stress, reactive oxygen species, photoreceptor outer segments, lipofuscin, macular pigment, lutein, zeaxanthin, alpha-tocopherol, antioxidant vitamins, macular pigment optical density, neovascular AMD, dietary antioxidants, risk factors
- MeSH terms
- Aging, Antioxidants, Ascorbic Acid, Humans, Macular Degeneration, Prognosis, Retina, Vitamin A, Vitamin E, Reactive Oxygen Species, Oxidative Stress
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