Abstract #5

by | Sep 25, 2023 | 2023 Abstracts

Abstract 5- 1100-1115
Category: Basic Science

At the end of the session, participants will be able to:

  1. Understand the axonal pathology in the retina in ALS.
  2. Describe the potential use of different non-invasive eye imaging modalities for assessing ocular biomarkers of ALS.
  3. Review the advantages and limitations of eye imaging biomarkers and their potential use in combination with other established biomarkers in ALS.

COI Disclosure:

None to disclose.

Presenter

Farbod Khorrami is a second-year MSc candidate at University of Toronto, conducting research at Yucel-Gupta Eye Pathology and Research Lab at St. Michael’s Hospital. He completed his undergraduate degree in U of T majoring in Neuroscience and Physiology. His graduate research focuses on developing a non-invasive ocular biomarker for amyotrophic lateral sclerosis (ALS).

Authors

Farbod Khorrami1,2*, Maryam Amin Mohammed Amin1*, Xun Zhou1, You Liang4, Neeru Gupta1-3,5, Yeni H. Yucel1-3, 5,6

1Keenan Research Centre for Biomedical Science, Unity Health Toronto. St. Michael’s Hospital, Toronto, ON, Canada
2Department of Laboratory Medicine & Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

3Department of Ophthalmology & Vision Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

4Department of Mathematics, Toronto Metropolitan University, Toronto, ON, Canada.

5Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.

6Institute of Biomedical Engineering, Science and Technology (iBEST), St. Michael’s Hospital, Toronto Metropolitan University, Toronto, ON, Canada.

    Target Audience:

    Pathologists, Residents, Medical Students

    CanMEDS:
    Communicator, Collaborator, Scholar

    Imaging Axonal Pathology In The Retina As A Potential Non-invasive Biomarker For Amyotrophic Lateral Sclerosis

    Imaging biomarkers of axonal pathology in amyotrophic lateral sclerosis (ALS) remain limited. We identified axonal spheroids, a pathological hallmark of ALS, in the post-mortem retina of ALS patients. We aim to establish the imaging of axonal pathology in the retina as a non-invasive ALS biomarker. Following ethics approval, 10 post-mortem ALS and 8 age-matched control eyes were imaged using a clinical eye imaging device (Spectralis, Heidelberg Engineering) combining confocal scanning laser ophthalmoscope and optical coherence tomography (OCT). Confocal microscopy imaging of phosphorylated neurofilament (P-NF) immunostained retinas was performed for histological validation.

    Sequential in vivo retinal imaging was performed in ALS mice (n=28) and age-matched controls (n=28) with Spectralis. Statistical analysis was performed using Generalized Linear Mixed Modeling (RStudio).

    Ex vivo human retinal fundus imaging (blue reflectance) detected more hyperreflective puncta in ALS patients compared to controls (19.04±22.5 vs. 2.7±1.6 /mm2, p<0.05). OCT confirmed puncta were localized in the retinal nerve fiber layer (RNFL).

    In vivo mouse fundus imaging (infrared reflectance) showed significantly more puncta in the retina of ALS mice, compared to controls (7.2±5.2 vs. 1.8±0.9, p<0.05), with a progressive increase over time in ALS mice (p<0.001). Immunofluorescence studies showed the presence of P-NF-positive axonal spheroids in the RNFL in human and mouse ALS retinas.

    Axonal pathology in ALS is detectable with a widely available clinical eye imaging device. This study suggests imaging of the axonal pathology in the eye is a promising biomarker for assessing ocular phenotype, progression, and treatment response in clinical trials in ALS.