Evidence map›Paper›PMID 37147305›Full record

ArticleNature communications2023

Single-cell analysis reveals inflammatory interactions driving macular degeneration.

Manik Kuchroo, Marcello DiStasio, Eric Song, Eda Calapkulu, Le Zhang, Maryam Ige, Amar H Sheth, Abdelilah Majdoubi, Madhvi Menon, Alexander Tong and 15 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
8.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 71 citations in OpenAlex.

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  10. The Raman Map of the Human Cell.Analytical chemistry · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 7 institutions in 4 countries.

Manik Kuchroo *Department of Neuroscience, Yale University, New Haven, CT, USA.
Marcello DiStasio *Department of Pathology, Yale University, New Haven, CT, USA.ORCID 0000-0001-6588-0713
Eric Song *Department of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.ORCID 0000-0001-5448-5865
Eda CalapkuluDepartment of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Le ZhangDepartment of Neuroscience, Yale University, New Haven, CT, USA.ORCID 0000-0002-4860-831X
Maryam IgeYale School of Medicine, New Haven, CT, USA.
Amar H ShethYale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-5002-5474
Abdelilah MajdoubiDepartment of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Madhvi MenonDivision of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK.
Alexander TongDepartment of Computer Science, Yale University, New Haven, CT, USA.ORCID 0000-0002-2031-4096
Abhinav GodavarthiDepartment of Applied Math, Yale University, New Haven, CT, USA.
Yu XingDepartment of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Scott GiganteComputational Biology, Bioinformatics Program, Yale University, New Haven, CT, USA.ORCID 0000-0002-4544-2764
Holly SteachDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Jessie HuangDepartment of Computer Science, Yale University, New Haven, CT, USA.
Guillaume HuguetMila-Quebec AI institute, Montréal, QC, Canada.ORCID 0000-0003-2126-5000
Janhavi NarainDepartment of Computer Science, Rutgers University, New Brunswick, NJ, USA.
Kisung YouDepartment of Genetics, Yale University, New Haven, CT, USA.
George MourgkosDepartment of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Rahul M DhodapkarYale School of Medicine, New Haven, CT, USA.
Matthew J HirnDepartment of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI, USA.ORCID 0000-0003-0290-4292
Bastian RieckDepartment of Biosystems Science and Engineering, ETH Zurich, Zurich, Switzerland.ORCID 0000-0003-4335-0302
Guy WolfMila-Quebec AI institute, Montréal, QC, Canada.ORCID 0000-0002-6740-059X
Smita KrishnaswamyDepartment of Computer Science, Yale University, New Haven, CT, USA. smita.krishnaswamy@yale.edu.ORCID 0000-0001-5823-1985
Brian P HaflerDepartment of Pathology, Yale University, New Haven, CT, USA. brian.hafler@yale.edu.ORCID 0000-0002-9263-3037
Yale University · USMila - Quebec Artificial Intelligence Institute · CABroad Institute · USETH Zurich · CHMichigan State University · USRutgers, The State University of New Jersey · USUniversity of Manchester · GB

Funding

Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Albert C Shaw · 2010 to 2026
$50.4M
Yale Core Grant for Vision ResearchP30EY026878 · NEI · YALE UNIVERSITY · PI Jonathan B Demb · 2016 to 2026
$7.1M
YALE CANCER CENTER CALABRESI IMMUNO-ONCOLOGY TRAINING PROGRAMK12CA215110 · NCI · YALE UNIVERSITY · PI Harriet M. Kluger · 2018 to 2026
$6.1M
Human and Translational Immunology Training ProgramT32AI155387 · NIAID · YALE UNIVERSITY · PI Joseph Edgar Craft, Kevan C Herold · 2021 to 2026
$2.6M
Short Term Research Training: Students in Health Professional SchoolsT35DK104689 · NIDDK · YALE UNIVERSITY · PI LLOYD G CANTLEY, Sarwat I Chaudhry · 2015 to 2026
$2.6M
Immune Network Dysregulation of the Central Nervous System with HIV Persistence and Opioid AbuseDP2DA056169 · NIDA · YALE UNIVERSITY · PI ZHANG, LE · 2022 to 2022
$2.5M
Sex-Specific Single Cell Expression Profiles, Genetic Risk and Drug Responsiveness in Alzheimer's DiseaseR56AG074015 · NIA · YALE UNIVERSITY · PI GHOSH, SOURAV, ROTHLIN, CARLA · 2021 to 2022
$2.5M
Targeting the inflammatory response in age-related macular degenerationR01EY034234 · NEI · YALE UNIVERSITY · PI Brian P Hafler · 2022 to 2026
$2.0M
Identification of the genetic pathways that give rise to the chicken rod-free zone and human fovea using epigenomic profilingK08EY026652 · NEI · YALE UNIVERSITY · PI HAFLER, BRIAN P · 2016 to 2020
$1.4M
Mechanisms of proinflammatory glial activation in retinal degenerationK08EY033013 · NEI · YALE UNIVERSITY · PI Marcello Michael DiStasio · 2024 to 2026
$842k
Characterizing Shared Features of Innate Immune Cells across Neurodegenerative Diseases using Single Cell Expression and Chromatin Accessibility DataF30AI157270 · NIAID · YALE UNIVERSITY · PI KUCHROO, MANIK · 2021 to 2022
$44k
NCI NIH HHS K12 CA215110NEI NIH HHS K08 EY026652NEI NIH HHS K08 EY033013NEI NIH HHS P30 EY026878NEI NIH HHS R01 EY034234NIAID NIH HHS F30 AI157270NIAID NIH HHS T32 AI155387NIAID NIH HHS U19 AI089992NIA NIH HHS R56 AG074015NIDA NIH HHS DP2 DA056169NIDDK NIH HHS T35 DK104689
6 · The paper itself

Abstract

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-1β 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.

Indexed as

Macular DegenerationNeurodegenerative DiseasesAnimalsHumansMiceNeurogliaRetinaSingle-Cell Analysis

Identifiers

PMID37147305
PMCPMC10162998
OpenAlexW4372334418

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.