September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Beta-Amyloid Deposition and Glial Changes in an APPPS1 Mouse Model of Alzheimer's Disease
Author Affiliations & Notes
  • Tanja Himmel
    Vetcore Facility for Research and Technology, University of Veterinary Medicine Vienna, Vienna, Austria
  • Stanislava Fialova
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Marco Augustin
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Bernhard Baumann
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Martin Glösmann
    Vetcore Facility for Research and Technology, University of Veterinary Medicine Vienna, Vienna, Austria
  • Footnotes
    Commercial Relationships   Tanja Himmel, None; Stanislava Fialova, None; Marco Augustin, None; Bernhard Baumann, None; Martin Glösmann, None
  • Footnotes
    Support  Austrian Science Fund FWF P25823-B24, European Research Council ERC Starting Grant 640396
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2240. doi:
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      Tanja Himmel, Stanislava Fialova, Marco Augustin, Bernhard Baumann, Martin Glösmann; Beta-Amyloid Deposition and Glial Changes in an APPPS1 Mouse Model of Alzheimer's Disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2240.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Overexpression of amyloid precursor protein (APP) and presenilin 1 (PS1) in APPPS1 mouse models for Alzheimer’s disease leads to early beta-amyloid plaque formation in the brain. It is controversial, however, whether beta-amyloid is also deposited in the retina. The aim of this study was to evaluate retinal beta-amyloid deposition in the APPPS1 mouse strain B6-Tg (Thy1-APPswe; Thy1-PS1 L166P) and its consequences for retinal cytoarchitecture.

Methods : Retinas and brains of 12 to 18-month-old APPPS1 transgenic mice (M. Jucker, Tübingen, Germany) and age-matched wildtype controls were processed for immunostaining. To visualize beta-amyloid-plaques, cryosections were stained with Congo red and examined using polarized light microscopy. Beta-amyloid antibodies and retinal cell type-specific markers were used to localize beta-amyloid deposits in retinas and brains. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) were applied to identify Müller cells and microglia, respectively. Anti-synaptophysin was used to evaluate synaptic integrity. Antibody binding and retinal structure was examined using widefield and confocal laser scanning microscopy.

Results : Unlike the brain, APPPS1 retinas were negative for congophilic birefringent material. Immunofluorescent labeling revealed robust cytoplasmic expression of beta-amyloid in retinal ganglion cells and a subset of amacrine cells. No extracellular beta-amyloid aggregates were observed. Overall, retinal layering and cytoarchitecture appeared unaffected in the APPPS1 mouse. However, Müller cells showed increased GFAP expression and microglia cells in the outer plexiform layer displayed processes extending to the outer limiting membrane in APPPS1 retinas.

Conclusions : In the APPPS1 retina, beta-amyloid is localized in retinal ganglion cells and amacrine cells. Extracellular amyloid plaques as observed in the brain are not displayed in the retina. The presence of activated glia cells indicates that beta-amyloid deposition in retinal neurons elicits neuroinflammatory responses. Future studies will be needed to elucidate why beta-amyloid forms plaques in the brain but not in the retina of this mouse model.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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