Viewing Ageing Eyes: Diverse Sites of Amyloid Beta Accumulation in the Ageing Mouse Retina and the Up-Regulation of Macrophages
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BACKGROUND: Amyloid beta (Aβ) accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD) in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse. METHODOLOGY/PRINCIPAL FINDINGS: We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation. CONCLUSIONS: Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The coating of Aβ on outer segments may also have an impact upon visual function with age.
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With advancing age, the outer retina displays elevated inflammation and widespread deposition of extracellular debris, including amyloid species.
“With advancing age, the outer retina of the eye displays elevated inflammation and widespread deposition of extracellular debris, including amyloid species [55, 88].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [55]
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- Authors
- Hoh Kam, J., Lenassi, E., & Jeffery, G.
- Affiliations
- Ljubljana University Medical Centre (SI)
- University College London (GB)
- Corresponding author
- Jeffery, Glen
- ORCID
- Jeffery, Glen
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-10-01
- Volume
- 5
- Issue
- 10
- Pages
- e13127
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2948519
- OpenAlex
- W1982572468
- Cited by
- 131
- References
- 65
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 14 · 2015: 10 · 2014: 8 · 2013: 11 · 2012: 12
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Rosetrees Trust
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyloid-beta, retinal aging, age-related macular degeneration, drusen, photoreceptor outer segments, Bruch's membrane, retinal macrophages, complement activation, mouse retina, photoreceptor degeneration, retinal blood flow
- MeSH terms
- Aging, Animals, Humans, Immunohistochemistry, Macrophage Activation, Macrophages, Macular Degeneration, Retina, Blotting, Western, Up-Regulation, Amyloid beta-Peptides, Mice
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