1. Noninvasive Antemortem Detection of Retinal Prions by a Fluorescent Tracer
- Author
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Aguilar-Calvo, Patricia, Sevillano, Alejandro M., Rasool, Suhail, Cao, Kevin J., Randolph, Lyndsay M., Rissman, Robert A., Sarraf, Stella T., Yang, Jerry, and Sigurdson, Christina J.
- Subjects
Amyloid beta-Peptides ,Prions ,General Neuroscience ,Amyloidogenic Proteins ,Neurodegenerative Diseases ,Amyloidosis ,General Medicine ,Article ,Retina ,Prion Diseases ,Cerebral Amyloid Angiopathy ,Mice ,Psychiatry and Mental health ,Clinical Psychology ,Alzheimer Disease ,Animals ,Longitudinal Studies ,Geriatrics and Gerontology - Abstract
Background: Neurodegenerative diseases are widespread yet challenging to diagnose and stage antemortem. As an extension of the central nervous system, the eye harbors retina ganglion cells vulnerable to degeneration, and visual symptoms are often an early manifestation of neurodegenerative disease. Objective: Here we test whether prion protein aggregates could be detected in the eyes of live mice using an amyloid-binding fluorescent probe and high-resolution retinal microscopy. Methods: We performed retinal imaging on an experimental mouse model of prion-associated cerebral amyloid angiopathy in a longitudinal study. An amyloid-binding fluorophore was intravenously administered, and retinal imaging was performed at timepoints corresponding to early, mid-, and terminal prion disease. Retinal amyloid deposits were quantified and compared to the amyloid load in the brain. Results: We report that by early prion disease (50% timepoint), discrete fluorescent foci appeared adjacent to the optic disc. By later timepoints, the fluorescent foci surrounded the optic disc and tracked along retinal vasculature. Conclusion: The progression of perivascular amyloid can be directly monitored in the eye by live imaging, illustrating the utility of this technology for diagnosing and monitoring the progression of cerebral amyloid angiopathy.
- Published
- 2022