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Kuchroo, Manik; DiStasio, Marcello; Song, Eric; Calapkulu, Eda; Zhang, Le; Ige, Maryam; Sheth, Amar H.; Majdoubi, Abdelilah; Menon, Madhvi; Tong, Alexander; Godavarthi, Abhinav; Xing, Yu; Gigante, Scott; Steach, Holly; Huang, Jessie; Huguet, Guillaume; Narain, Janhavi; You, Kisung; Mourgkos, George; Dhodapkar, Rahul M.; Hirn, Matthew J.; Rieck, Bastian; Wolf, Guy; Krishnaswamy, Smita;

Single-cell analysis reveals inflammatory interactions driving macular degeneration

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  • Media type: E-Article
  • Title: Single-cell analysis reveals inflammatory interactions driving macular degeneration
  • Contributor: Kuchroo, Manik; DiStasio, Marcello; Song, Eric; Calapkulu, Eda; Zhang, Le; Ige, Maryam; Sheth, Amar H.; Majdoubi, Abdelilah; Menon, Madhvi; Tong, Alexander; Godavarthi, Abhinav; Xing, Yu; Gigante, Scott; Steach, Holly; Huang, Jessie; Huguet, Guillaume; Narain, Janhavi; You, Kisung; Mourgkos, George; Dhodapkar, Rahul M.; Hirn, Matthew J.; Rieck, Bastian; Wolf, Guy; Krishnaswamy, Smita;
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-023-37025-7
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Due to commonalities in pathophysiology, age-related macular degeneration (AMD) 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 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. 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-1<jats:italic>β</jats:italic> which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.</jats:p>
  • Access State: Open Access