Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration
Open accessAbstract
Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1(-/-) mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1(-/-) mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1(-/-) mice showed oxidative damage, and their beta-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1(-/-) mouse is a valuable animal model to study human age-related macular degeneration.
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Mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD.
“and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2008; Ufret-Vincenty et al., 2010).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Imamura et al., 2006
At 10 months of age, 86% of Sod1−/− mice had drusen, compared to very few drusen in age-matched wild-type mice.
“At 10 months of age, 86% of mice had drusen, compared to very few drusen in age-matched wild-type mice (Imamura et al., 2006).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Imamura et al., 2006
Bruch's membrane was markedly thickened, with a thickness approximately 6-fold greater in Sod1−/− mice compared to age-matched wild-type mice.
“Bruch’s membrane was markedly thickened, with a thickness approximately 6-fold greater in Sod1−/− mice compared to age-matched wild-type mice.”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Imamura et al., 2006
Imamura et al. showed that Sod1−/− mice have accelerated age-related pathologic changes in the retina reminiscent of AMD, including drusen, thickening of Bruch's membrane, and CNV.
“Imamura et al. showed that Sod1−/− mice have accelerated age-related pathologic changes in the retina reminiscent of AMD, including drusen, thickening of Bruch’s membrane, and CNV (Imamura et al., 2006).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Imamura et al., 2006
Approximately 10% of Sod1−/− mice older than 10 months had CNV.
“Approximately 10% of mice older than 10 months had CNV (Imamura et al., 2006).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Imamura et al., 2006
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- Authors
- Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., & Tsubota, K.
- Affiliations
- Keio University (JP)
- Tokai University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Jikei University School of Medicine (JP)
- Tokyo Dental College (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-07-25
- Volume
- 103
- Issue
- 30
- Pages
- 11282-11287
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2020391754
- Cited by
- 420
- References
- 47
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 13 · 2023: 23 · 2022: 18 · 2021: 20 · 2020: 26 · 2019: 11 · 2018: 21 · 2017: 22 · 2016: 16 · 2015: 18 · 2014: 25 · 2013: 24 · 2012: 38
- FWCI
- 20.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- 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
- age-related macular degeneration, superoxide dismutase, oxidative stress, drusen, choroidal neovascularization, retinal pigment epithelium, Bruch's membrane, β-catenin, tight junctions, free radical theory of aging
- MeSH terms
- Superoxide Dismutase-1, Animals, Disease Models, Animal, Light, Macular Degeneration, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Pigment Epithelium of Eye, Superoxide Dismutase, Optic Disk Drusen, Choroid Diseases, Oxidative Stress, beta Catenin, Mice
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