June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Comparative retinal imaging in mouse models of proteinopathies identifies disease-specific biomarkers
Author Affiliations & Notes
  • Lies De Groef
    Department of Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Lien Veys
    Department of Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Marjan Vandenabeele
    Department of Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Xavier Hadoux
    Centre for Eye Research Australia Ltd, East Melbourne, Victoria, Australia
  • Sophie Lemmens
    Katholieke Universiteit Leuven Universitaire Ziekenhuizen Leuven Campus Gasthuisberg Dienst Ophthalmology, Leuven, Flanders, Belgium
  • Lutgarde Serneels
    Katholieke Universiteit Leuven Groep Biomedische Wetenschappen, Leuven, Flanders, Belgium
  • Jan Theunis
    VITO NV, Mol, Antwerpen, Belgium
  • Bart De Strooper
    Katholieke Universiteit Leuven Groep Biomedische Wetenschappen, Leuven, Flanders, Belgium
  • Ingeborg Stalmans
    Katholieke Universiteit Leuven Universitaire Ziekenhuizen Leuven Campus Gasthuisberg Dienst Ophthalmology, Leuven, Flanders, Belgium
  • Peter van Wijngaarden
    Centre for Eye Research Australia Ltd, East Melbourne, Victoria, Australia
  • Lieve K M Moons
    Department of Biology, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
  • Footnotes
    Commercial Relationships   Lies De Groef, None; Lien Veys, None; Marjan Vandenabeele, None; Xavier Hadoux, Enlighten Imaging PTY LTD (P); Sophie Lemmens, None; Lutgarde Serneels, None; Jan Theunis, None; Bart De Strooper, None; Ingeborg Stalmans, None; Peter van Wijngaarden, Enlighten Imaging PTY LTD (P); Lieve Moons, None
  • Footnotes
    Support  MV, LV and LDG are fellows of the Research Foundation Flanders (FWO). This research was supported by the Alzheimer’s Research Foundation (SAO-FRA), the European Union Horizon 2020 Research and Innovation Program (2014-2020) (HERALD project, granted by the ATTRACT consortium). The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government. XH and PvW acknowledge funding support from the H & L Hecht Trust and the Yulgilbar Alzheimer’s Research Program.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 364. doi:
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      Lies De Groef, Lien Veys, Marjan Vandenabeele, Xavier Hadoux, Sophie Lemmens, Lutgarde Serneels, Jan Theunis, Bart De Strooper, Ingeborg Stalmans, Peter van Wijngaarden, Lieve K M Moons; Comparative retinal imaging in mouse models of proteinopathies identifies disease-specific biomarkers. Invest. Ophthalmol. Vis. Sci. 2021;62(8):364.

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

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Abstract

Purpose : In previous research we have shown that the AppNL-G-F mouse retina mimics the early, preclinical stages of Alzheimer’s disease, and that retinal imaging offers unique opportunities for research and drug discovery [1] . In this follow-up study, we have used in vivo and ex vivo retinal imaging in conjunction with immunohistochemistry and molecular assays, in a range of mouse models of neurodegenerative diseases characterized by protein aggregation, to identify the pathological correlates of imaging biomarkers.

Methods : Mouse models of alpha-synuclein, tau, and amyloid overexpression/aggregation underwent a battery of retinal examinations, including in vivo optical coherence tomography and electroretinography as well as ex vivo hyperspectral imaging (HSI; Snapscan, Imec). HSI spectra were analyzed as previously described [1]. Retinal samples were collected for immunohistochemistry and molecular studies of protein aggregation.

Results : Diverging patterns of retinal dysfunction and/or degeneration were observed in the different mouse models, illustrating the varied impacts of these protein aggregates on retinal structure and function. Moreover, while all protein aggregates led to HSI changes in the 450-600 nm range, distinct signatures were observed. Immunohistochemical and molecular studies revealed that the observed HSI changes correlated both with levels of the protein aggregates that are the hallmarks of these diseases, and with levels of soluble oligomers.

Conclusions : HSI can be used to quantify retinal amyloid beta, underscoring its potential as a biomarker for Alzheimer’s diagnosis and disease monitoring. Moreover, our research indicates that the HSI signatures of alpha-synuclein, tau, and amyloid aggregates are distinct. These findings add further evidence to suggest that retinal HSI may have utility in the diagnosis and stratification of proteinopathies associated with the most common forms of human neurodegenerative diseases.

[1] Vandenabeele et al. (2021) Acta Neuropathologica Communications [https://rdcu.be/cdbmS]

This is a 2021 ARVO Annual Meeting abstract.

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