Evidence map›Paper›PMID 34544431›Full record

ArticleJournal of neuroinflammation2021

Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure.

Keith E Campagno, Wennan Lu, Assraa Hassan Jassim, Farraj Albalawi, Aurora Cenaj, Huen-Yee Tso, Sophia P Clark, Puttipong Sripinun, Néstor Más Gómez, Claire H Mitchell

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
8.5field-weighted citation impact, top 1% 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

32 citing papers in PubMed, 66 citations in OpenAlex.

  1. Review
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  8. The P2X7 Receptor Regulates IL-1β Secretion in the Human Retina.International journal of molecular sciences · 2025
    Article
  9. Article
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  14. MgSOFrontiers in nutrition · 2025
    Article
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  19. Article
  20. The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024
    Review
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 2 institutions in 2 countries.

Keith E CampagnoDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Wennan LuDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Assraa Hassan JassimDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Farraj AlbalawiDepartment of Orthodontics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Aurora CenajDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Huen-Yee TsoDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Sophia P ClarkDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Puttipong SripinunDepartment of Orthodontics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Néstor Más GómezDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA.
Claire H MitchellDepartment of Basic and Translational Science, University of Pennsylvania, 240 S. 40th St, Philadelphia, PA, 19104, USA. chm@upenn.edu.ORCID http://orcid.org/0000-0002-9784-6672
University of Pennsylvania · USKing Saud bin Abdulaziz University for Health Sciences · SA

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
NRSA Training CoreTL1TR001880 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MEAGHER, EMMA ANNE · 2016 to 2025
$10.0M
Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
BRIAN INJURY TRAINING GRANTT32NS043126 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Douglas Hamilton Smith · 2003 to 2026
$5.9M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
RESEARCH ON NORMAL AND ABNORMAL MECHANISMS OF VISIONST32EY007035 · NEI · UNIVERSITY OF PENNSYLVANIA · PI Diego Contreras, Jessica I.W. Morgan · 1985 to 2026
$4.9M
NCATS NIH HHS TL1 TR001880NCATS NIH HHS TL1TR001880NEI NIH HHS EY-013434NEI NIH HHS EY-015537NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY015537NEI NIH HHS T32 EY007035NEI NIH HHS T32EY007035NINDS NIH HHS T32 NS043126NINDS NIH HHS T32NS043126
6 · The paper itself

Abstract

backgroundThe identification of endogenous signals that lead to microglial activation is a key step in understanding neuroinflammatory cascades. As ATP release accompanies mechanical strain to neural tissue, and as the P2X7 receptor for ATP is expressed on microglial cells, we examined the morphological and molecular consequences of P2X7 receptor stimulation in vivo and in vitro and investigated the contribution of the P2X7 receptor in a model of increased intraocular pressure (IOP).

methodsIn vivo experiments involved intravitreal injections and both transient and sustained elevation of IOP. In vitro experiments were performed on isolated mouse retinal and brain microglial cells. Morphological changes were quantified in vivo using Sholl analysis. Expression of mRNA for M1- and M2-like genes was determined with qPCR. The luciferin/luciferase assay quantified retinal ATP release while fura-2 indicated cytoplasmic calcium. Microglial migration was monitored with a Boyden chamber.

resultsSholl analysis of Iba1-stained cells showed retraction of microglial ramifications 1 day after injection of P2X7 receptor agonist BzATP into mouse retinae. Mean branch length of ramifications also decreased, while cell body size and expression of Nos2, Tnfa, Arg1, and Chil3 mRNA increased. BzATP induced similar morphological changes in ex vivo tissue isolated from Cx3CR1

conclusionsP2X7 receptor stimulation induced rapid morphological activation of microglial cells, including process retraction and cell body enlargement, and upregulation of markers linked to both M1- and M2-type activation. Parallel responses accompanied IOP elevation, suggesting ATP release and P2X7 receptor stimulation influence the early microglial response to increased pressure.

Indexed as

AnimalsGlaucomaMiceMice, Inbred C57BLMicrogliaReceptors, Purinergic P2X7Up-RegulationReceptors, Purinergic P2X7ATP releaseChemoattraction migrationGlaucomaIba1Intraocular pressureMicroglial M1/M2 activationNeuroinflammationP2X7 receptorP2Y12 receptorSholl analysisTraumatic brain injury

Identifiers

PMID34544431
PMCPMC8454080
OpenAlexW3201220696

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.