June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Amyotrophic Lateral Sclerosis Mice Eyes Reveal Retinal Nerve Fiber Layer Changes Over Time: An In Vivo Imaging Study
Author Affiliations & Notes
  • Farbod Khorrami
    Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
    Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
  • Neeru Gupta
    Department of Ophthalmology and Visual Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
    Department of Ophthalmology and Vision Sciences, University of Toronto, St. Michael's Hospital, Keenan Research Centre for Biomedical Science, Toronto, Ontario, Canada
  • Xun Zhou
    Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
  • You Liang
    Department of Mathematics, Toronto Metropolitan University, Toronto, Ontario, Canada
  • Yeni H Yucel
    Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
    Department of Ophthalmology and Vision Sciences, and Laboratory Medicine and Pathobiology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Farbod Khorrami None; Neeru Gupta None; Xun Zhou None; You Liang None; Yeni Yucel None
  • Footnotes
    Support  ALS Canada Research Program and Canada Brain Foundation Discovery Grant (YHY, NG), Ron and Alayne Metrick Research Fund (YHY, NG), Henry S. Farrugia Ophthalmic Research Fund (YHY, NG), Dan Sullivan Research Fund (YHY, NG), Canada Foundation for Innovation Leaders Opportunity Fund (31326, YHY, NG), Canadian Institutes of Health Research (FK), Vision Science Research Program (FK)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2309. doi:
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    • Get Citation

      Farbod Khorrami, Neeru Gupta, Xun Zhou, You Liang, Yeni H Yucel; Amyotrophic Lateral Sclerosis Mice Eyes Reveal Retinal Nerve Fiber Layer Changes Over Time: An In Vivo Imaging Study. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2309.

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

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Abstract

Purpose : Amyotrophic Lateral Sclerosis (ALS) is a disease characterized by degeneration of motor neurons without any cure. An accessible and non-invasive biomarker for ALS is urgently needed for clinical trials. We recently discovered axonal spheroids in the retinal nerve fiber layer (RNFL) in post-mortem eyes of ALS patients which are comparable to spheroids seen in motor neurons of ALS patients1. We conducted a longitudinal in vivo imaging study to determine whether similar retinal changes can be detected in a commonly used ALS mouse model.

Methods : In vivo eye imaging of ALS mice (ALS mouse model SOD1G93A, 2 months old, n=12, 6M, 6F) and age-matched control mice (C57BL/6J, n=12, 6M, 6F) was performed biweekly for 12 weeks. Spectralis (Heidelberg Engineering) with Confocal Scanning Laser Ophthalmoscope (cSLO) with infrared (IR, 815 nm) and Blue Reflectance (BR, 488 nm) modalities and Optical Coherence Tomography (OCT, 870 nm) were used for each imaging session. The fundus was observed with cSLO, and OCT was used to validate puncta location in the RNFL. Retinal fundus puncta localized in the RNFL by OCT were counted in both retinas in a masked fashion. Intraocular pressure, body weight, and ALS clinical motor scoring were performed weekly. Changes in the number of profiles over time were analyzed using a Generalized Linear Mixed-Effect Model (GLMM, RStudio 2022.07.1).

Results : Infrared cSLO imaging of the ALS mouse eyes revealed discrete hyperreflective bodies within the RNFL. Compared to age-matched controls, a significant increase in the number of hyperreflective puncta was observed at all time points and increased significantly from 2 months to 5 months (p = 0.023). By week 12, ALS mice showed 8 ± 8.4 bodies in both retinas compared to age-matched control mice which showed 0.25 ± 0.62 (p < 0.001). The results from the GLMM showed that ALS mutation (p < 0.001) and gender (p = 0.003) were statistically significant features that affect the hyperreflective puncta growth curve over time.

Conclusions : The findings of discrete pathological bodies in the retinal nerve fiber layer of the mouse ALS eye, and their significant increase with age points to a potential biomarker of axonal degeneration in ALS.

1. Sharma, K. et al. Retinal Spheroids and Axon Pathology Identified in Amyotrophic Lateral Sclerosis. Invest. Ophthalmol. Vis. Sci. 61, 30 (2020).

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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