Cited by 303Alzheimer's disease research and treatmentsRetinal Diseases and TreatmentsGlaucoma and retinal disorders

Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease

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Ning, Allison, Cui, Jing, To, Eleanor, Ashe, Karen Hsiao, Matsubara, Joanne·2008·Investigative Opthalmology & Visual Science

Abstract

PURPOSE: To compare the temporal and spatial expression patterns of amyloid precursor protein (APP), amyloid-beta deposits, inflammatory chemokines, and apoptosis in the retina of a mouse model of Alzheimer disease (AD). METHODS: Retinas of transgenic mice harboring a mutant presenilin (PS1) and a mutant APP gene were processed for TUNEL and immunohistochemistry with antibodies against APP, amyloid-beta, monocyte chemotactic protein (MCP)-1, and F4/80. Comparisons were made between age groups and between transgenic and wild-type congeners. RESULTS: The neuroretina demonstrated age-dependent increases in APP in the ganglion cells (RGCs) and in neurons of the inner nuclear layer (INL). Amyloid-beta demonstrated significant age-dependent deposition in the nerve fiber layer (NFL). TUNEL-positive RGC increased in an age-dependent fashion and in transgenic compared with wild-type congeners. Concomitant overexpression of MCP-1 and intense immunoreactivity for F4/80 suggested that RGCs upregulate MCP-1 in response to amyloid-beta. Activated microglia proliferated in response to MCP-1. In the outer retina, retinal pigment epithelium (RPE) demonstrated moderate age-dependent APP immunoreactivity, but nearby drusenlike deposits were not present. Amyloid-beta was observed in the choriocapillaris of the older animals. CONCLUSIONS: Amyloid-beta deposits accumulate with age in the retina of a transgenic mouse model of AD. The amyloid-beta loads are accompanied by increased immunoreactivity for MCP-1, F4/80, and TUNEL-positive profiles in the RGC layer. The results suggest that amyloid-beta causes neurodegeneration in the retina of the doubly mutant transgenic mouse model of AD.

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  1. [36]Green RG, Harlan JB. Histopathologic features. In: Berger JW, Fine SL, Maguire MG, editors. Age-Related Macular Degeneration. St. Louis, MO: Mosby; 1999. pp. 81–154. [Google Scholar]

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Authors
Ning, A., Cui, J., To, E., Ashe, K. H., & Matsubara, J.
Affiliations
  • University of British Columbia (CA)
  • University of Minnesota (US)
Venue
Investigative Opthalmology & Visual Science
Published
2008-11-01
Volume
49
Issue
11
Pages
5136
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
OpenAlex
W2007162302
Cited by
303
References
54
Citations by year
2026: 7 · 2025: 16 · 2024: 17 · 2023: 17 · 2022: 25 · 2021: 25 · 2020: 27 · 2019: 11 · 2018: 28 · 2017: 14 · 2016: 21 · 2015: 20 · 2014: 15 · 2013: 8 · 2012: 19
FWCI
7.45
Type
journal article
Language
en
Open access
Locations
  • Investigative Ophthalmology & Visual Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Canadian Institutes of Health Research (77736_2, 77736_1, 97806_1)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
Keywords
amyloid-beta deposition, retinal degeneration, Alzheimer's disease, amyloid precursor protein, retinal ganglion cells, microglial activation, MCP-1, apoptosis, retinal pigment epithelium, choriocapillaris, transgenic mouse model, neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Antigens, Differentiation, Disease Models, Animal, Immunohistochemistry, Membrane Glycoproteins, Mice, Transgenic, Retina, Retinal Degeneration, Biomarkers, Amyloid beta-Peptides, Apoptosis, Chemokine CCL2, In Situ Nick-End Labeling, Mice

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