July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Ocular biomarkers of Alzheimer’s disease (AD): Distribution of amyloid-beta in human AD and non-AD retina
Author Affiliations & Notes
  • Qinyuan (Alis) Xu
    University of British Columbia, Vancouver, British Columbia, Canada
  • Sieun Lee
    University of British Columbia, Vancouver, British Columbia, Canada
    School of Engineering, Simon Fraser University, British Columbia, Canada
  • Veronica Hirsch-Reinshagen
    University of British Columbia, Vancouver, British Columbia, Canada
  • Ian Mackenzie
    University of British Columbia, Vancouver, British Columbia, Canada
  • Robin Hsiung
    University of British Columbia, Vancouver, British Columbia, Canada
  • Geoffrey Charm
    University of British Columbia, Vancouver, British Columbia, Canada
  • Elliott To
    University of British Columbia, Vancouver, British Columbia, Canada
  • Kailun Jiang
    University of British Columbia, Vancouver, British Columbia, Canada
  • Marinko V Sarunic
    School of Engineering, Simon Fraser University, British Columbia, Canada
  • Mirza Faisal Beg
    School of Engineering, Simon Fraser University, British Columbia, Canada
  • Jing Z Cui
    University of British Columbia, Vancouver, British Columbia, Canada
  • Eleanor To
    University of British Columbia, Vancouver, British Columbia, Canada
  • Joanne A Matsubara
    University of British Columbia, Vancouver, British Columbia, Canada
  • Footnotes
    Commercial Relationships   Qinyuan (Alis) Xu, None; Sieun Lee, None; Veronica Hirsch-Reinshagen, None; Ian Mackenzie, None; Robin Hsiung, None; Geoffrey Charm, None; Elliott To, None; Kailun Jiang, None; Marinko Sarunic, None; Mirza Beg, None; Jing Cui, None; Eleanor To, None; Joanne Matsubara, None
  • Footnotes
    Support  Brain Canada, Genome BC, CIHR, UBC Faculty of Medicine
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6006. doi:
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      Qinyuan (Alis) Xu, Sieun Lee, Veronica Hirsch-Reinshagen, Ian Mackenzie, Robin Hsiung, Geoffrey Charm, Elliott To, Kailun Jiang, Marinko V Sarunic, Mirza Faisal Beg, Jing Z Cui, Eleanor To, Joanne A Matsubara; Ocular biomarkers of Alzheimer’s disease (AD): Distribution of amyloid-beta in human AD and non-AD retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6006.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Earlier studies reported the existence of amyloid-β (Aβ) protein, the pathological hallmark of Alzheimer’s disease (AD), in the human retina. Our group has previously described the laminar distribution and cellular compartment of Aβ protein in the AD and normal human retina. Upregulation of retinal supporting cells such as astrocytes, microglia, and Müller cells are important processes in many retinal diseases. Retinal localization of Aβ and its relationship to these cellular profiles in AD are poorly understood. This study further describes the cellular localization of Aβ deposits in relation to the neuronal and glial populations in the AD and normal human retina.

Methods : Post-mortem human retinal tissue from AD donors and age-matched normal donors were processed. Retinal samples were processed as free-floating punches (4 mm diameter) or paraffin embedded cross-sections (5 um thickness) using immunochemistry. Antibodies against TUBB and GFAP were used to label neurons and astrocytes, respectively. Confocal microscopy was used to visualize the results. Representative images are taken for both retinal punches and cross-sectional samples in all experimental groups. In the cross-sectional images, retinal layers were segmented using ITK-SNAP software, and quantitative parameters were computed, including average layer thickness and normalized layer-wise measurements of immunostaining density and Aβ colocalization percentage.

Results : Preliminary results show a higher percentage of Aβ colocalizing to TUBB labeled neurons compared to GFAP labeled astrocytes. On average, 20.8% of TUBB-positive pixels were Aβ-positive in AD donors, compared to 13.3% in controls. 8.36% of GFAP-positive pixels were Aβ-positive in AD donors and 2.86% in controls.

Conclusions : We quantified the distribution of Aβ-immunoreactive profiles in the AD and normal human retina in relation to neurons and astrocytes. Aβ depositions were found to preferentially colocalize with neurons rather than astrocytes. Future directions include assessing the colocalization of Aβ-immunoreactive profiles with retinal microglial cells, another important cell type associated with AD pathology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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