Publication Date
11-4-2024
Journal
Journal of Experimental Medicine
DOI
10.1084/jem.20240386
PMID
39316084
PMCID
PMC11448872
PubMedCentral® Posted Date
9-24-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Alzheimer Disease, Animals, Amyloid beta-Peptides, Humans, Mice, Transgenic, Retinal Degeneration, Brain, Mice, Aquaporin 4, Glymphatic System, Retina, Optic Nerve, Male, Female, Disease Models, Animal, Mice, Inbred C57BL, Aged
Abstract
The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered β-amyloid (Aβ) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aβ from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aβ is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aβ transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aβ in brain-eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aβ induced damage and visual impairment. These results revealed brain-to-eye Aβ transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.