Evidence map›Paper›PMID 31170999›Full record

ArticleJournal of neuroinflammation2019

Reactive microglia and IL1β/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina.

Levi Todd, Isabella Palazzo, Lilianna Suarez, Xiaoyu Liu, Leo Volkov, Thanh V Hoang, Warren A Campbell, Seth Blackshaw, Ning Quan, Andy J Fischer

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
8.5field-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

98 citing papers in PubMed, 177 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. IL1A enhances TNF-induced retinal ganglion cell death.Frontiers in aging neuroscience · 2026
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  6. The Immunopathogenesis of uveitis.Frontiers in medicine · 2026
    Review
  7. Article
  8. Review
  9. The P2X7 Receptor Regulates IL-1β Secretion in the Human Retina.International journal of molecular sciences · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. The neuroimmune interface in retinal regeneration.Progress in retinal and eye research · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

38 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 1 country.

Levi ToddDepartment of Biological Structure, University of Washington, Seattle, WA, USA.
Isabella PalazzoDepartment of Neuroscience, College of Medicine, The Ohio State University, 3020 Graves Hall, 333 W. 10th Ave, Columbus, OH, 43210-1239, USA.
Lilianna SuarezDepartment of Neuroscience, College of Medicine, The Ohio State University, 3020 Graves Hall, 333 W. 10th Ave, Columbus, OH, 43210-1239, USA.
Xiaoyu LiuInstitute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH, USA.
Leo VolkovDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Thanh V HoangSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Warren A CampbellDepartment of Neuroscience, College of Medicine, The Ohio State University, 3020 Graves Hall, 333 W. 10th Ave, Columbus, OH, 43210-1239, USA.
Seth BlackshawSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ning QuanInstitute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH, USA.
Andy J FischerDepartment of Neuroscience, College of Medicine, The Ohio State University, 3020 Graves Hall, 333 W. 10th Ave, Columbus, OH, 43210-1239, USA. Andrew.Fischer@osumc.edu.ORCID http://orcid.org/0000-0001-6123-7405
The Ohio State University · USInstitute for Behavioral Medicine · USJohns Hopkins University · USUniversity of Washington · USWashington University in St. Louis · US

Funding

Transcriptional regulation of retinal cell differentiation and functionR01EY020560 · NEI · JOHNS HOPKINS UNIVERSITY · PI BLACKSHAW, SETH · 2011 to 2021
$4.4M
Muller glia: roles in retinal homeostasis and neuronal regenerationR01EY022030 · NEI · OHIO STATE UNIVERSITY · PI FISCHER, ANDY J · 2012 to 2021
$3.5M
Comparative transcriptomic and epigenomic analyses of Muller glia reprogrammingU01EY027267 · NEI · UNIVERSITY OF NOTRE DAME · PI BLACKSHAW, SETH, HYDE, DAVID R · 2016 to 2019
$3.0M
Anxiety, IL-1R1 and neuroinflammationR01MH109165 · NIMH · OHIO STATE UNIVERSITY · PI QUAN, NING · 2016 to 2020
$1.9M
NEI NIH HHS R01 EY020560NEI NIH HHS R01 EY022030NEI NIH HHS RO1 EY022030-06NEI NIH HHS U01 EY027267NEI NIH HHS UO1 EY027267-02NIMH NIH HHS R01 MH109165NIMH NIH HHS R01 MH109165-01
6 · The paper itself

Abstract

backgroundMicroglia and inflammation have context-specific impacts upon neuronal survival in different models of central nervous system (CNS) disease. Herein, we investigate how inflammatory mediators, including microglia, interleukin 1 beta (IL1β), and signaling through interleukin 1 receptor type 1 (IL-1R1), influence the survival of retinal neurons in response to excitotoxic damage.

methodsExcitotoxic retinal damage was induced via intraocular injections of NMDA. Microglial phenotype and neuronal survival were assessed by immunohistochemistry. Single-cell RNA sequencing was performed to obtain transcriptomic profiles. Microglia were ablated by using clodronate liposome or PLX5622. Retinas were treated with IL1β prior to NMDA damage and cell death was assessed in wild type, IL-1R1 null mice, and mice expressing IL-1R1 only in astrocytes.

resultsNMDA-induced damage included neuronal cell death, microglial reactivity, upregulation of pro-inflammatory cytokines, and genes associated with IL1β-signaling in different types of retinal neurons and glia. Expression of the IL1β receptor, IL-1R1, was evident in astrocytes, endothelial cells, some Müller glia, and OFF bipolar cells. Ablation of microglia with clodronate liposomes or Csf1r antagonist (PLX5622) resulted in elevated cell death and diminished neuronal survival in excitotoxin-damaged retinas. Exogenous IL1β stimulated the proliferation and reactivity of microglia in the absence of damage, reduced numbers of dying cells in damaged retinas, and increased neuronal survival following an insult. IL1β failed to provide neuroprotection in the IL-1R1-null retina, but IL1β-mediated neuroprotection was rescued when expression of IL-1R1 was restored in astrocytes.

conclusionsWe conclude that reactive microglia provide protection to retinal neurons, since the absence of microglia is detrimental to survival. We propose that, at least in part, the survival-influencing effects of microglia may be mediated by IL1β, IL-1R1, and interactions of microglia and other macroglia.

Indexed as

AnimalsExcitatory Amino Acid AgonistsInflammationInterleukin-1betaMiceMice, Inbred C57BLMice, KnockoutMicrogliaNeuroprotectionNeurotoxinsN-MethylaspartateReceptors, Interleukin-1 Type IRetinaExcitatory Amino Acid AgonistsIL1R1 protein, mouseInterleukin-1betaNeurotoxinsN-MethylaspartateReceptors, Interleukin-1 Type IIL-1R1IL1βMicrogliaRetinal neuroprotection

Identifiers

PMID31170999
PMCPMC6555727
OpenAlexW2948077003

What OpenQuestion holds

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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 OpenQuestion graph.