Single-cell analysis reveals inflammatory interactions driving macular degeneration

ABSTRACT: Due to commonalities in pathophysiology, age-related macular degeneration represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 17 retinas with age-related macular degeneration and controls. We create a machine learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer’s disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1beta which drives angiogenesis characteristic of disease pathogenesis. Thus, due to shared glial states, the retina provides a system for investigating therapeutic approaches in neurodegenerative diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221042 | GEO | 2023/01/18

REPOSITORIES: GEO