A Retinal Biophysical Biomarker for Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease with no current valid diagnostic imaging biomarkers. The retina is an extension of the central nervous system and axonal transport defects have been documented in various neurodegenerative diseases. This study reports evidence of axonal pathology in the retina of ALS patients using an interdisciplinary approach that includes the neuropathological study of retinal sections in ALS patients expanded to the optical characteristics of the whole retina preparations using eye imaging technology. The histopathological examination of retina sections revealed round profiles in the retinal nerve fibre layer in 10 out 10 ALS patients and in 4 out of 10 age-matched control patients. All 10 ALS patients showed increased phosphorylated neurofilament immunoreactivity in the retinal nerve fibre layer compared to all 10 control patients. Retinal imaging of whole globes and retina flat-mounts by blue reflectance retinal funduscopy and optical coherence tomography revealed hyper-reflective profiles in the retinal nerve fibre layer. For the first time, approximately 1µm retinal ganglion cells axons were visualized in immunofluorescence stained retina flat-mounts using near-infrared retina fundus imaging and Image Mapping Spectrometer. These findings suggest axonal pathology in retinal ganglion cells and its potential use as a novel non-invasive ocular imaging biomarker for ALS.