Evidence map›Paper›PMID 34446062›Full record

ArticleJournal of neuroinflammation2021

Inflammatory resolution and vascular barrier restoration after retinal ischemia reperfusion injury.

Steven F Abcouwer, Sumathi Shanmugam, Arivalagan Muthusamy, Cheng-Mao Lin, Dejuan Kong, Heather Hager, Xuwen Liu, David A Antonetti

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 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
11.3field-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

57 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Key immune regulators in retinal ischemia-reperfusion injuryInternational journal of ophthalmology · 2025
    Article
  19. Monocytes in Retinal Degeneration: Little Cells with a Big Impact.Advances in experimental medicine and biology · 2025
    Review
  20. Article
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

8 authors at 1 institution in 1 country.

Steven F AbcouwerDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA. sabcouwe@umich.edu.ORCID http://orcid.org/0000-0003-2580-1288
Sumathi ShanmugamDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
Arivalagan MuthusamyEsperovax Inc., Plymouth, MI, 48170, USA.
Cheng-Mao LinDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
Dejuan KongDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
Heather HagerDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
Xuwen LiuDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
David A AntonettiDepartment of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, MI, 48105, USA.
University of Michigan · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
VIVARIUM MODULEP30EY007003 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti · 1987 to 2026
$17.6M
Unraveling the role of tPA in the neurovascular unitR01HL055374 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti, Daniel A Lawrence · 1995 to 2026
$8.6M
MECHANISMS OF RETINAL VASCULAR PERMEABILITY IN DIABETESR01EY012021 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANTONETTI, DAVID · 1998 to 2024
$8.6M
Inflammatory Resolution and Vascular Restoration in Diabetic RetinopathyR01EY029349 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABCOUWER, STEVEN F, ANTONETTI, DAVID · 2018 to 2022
$2.4M
NEI NIH HHS P30 EY007003NEI NIH HHS P30EY007003NEI NIH HHS R01 EY012021NEI NIH HHS R01 EY029349NEI NIH HHS R01EY029349NHLBI NIH HHS R01 HL055374NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30DK020572Research to Prevent Blindness None
6 · The paper itself

Abstract

backgroundSeveral retinal pathologies exhibit both inflammation and breakdown of the inner blood-retinal barrier (iBRB) resulting in vascular permeability, suggesting that treatments that trigger resolution of inflammation may also promote iBRB restoration.

methodsUsing the mouse retinal ischemia-reperfusion (IR) injury model, we followed the time course of neurodegeneration, inflammation, and iBRB disruption and repair to examine the relationship between resolution of inflammation and iBRB restoration and to determine if minocycline, a tetracycline derivative shown to reverse microglial activation, can hasten these processes.

resultsA 90-min ischemic insult followed by reperfusion in the retina induced cell apoptosis and inner retina thinning that progressed for approximately 2 weeks. IR increased vascular permeability within hours, which resolved between 3 and 4 weeks after injury. Increased vascular permeability coincided with alteration and loss of endothelial cell tight junction (TJ) protein content and disorganization of TJ protein complexes. Shunting of blood flow away from leaky vessels and dropout of leaky capillaries were eliminated as possible mechanisms for restoring the iBRB. Repletion of TJ protein contents occurred within 2 days after injury, long before restoration of the iBRB. In contrast, the eventual re-organization of TJ complexes at the cell border coincided with restoration of the barrier. A robust inflammatory response was evident a 1 day after IR and progressed to resolution over the 4-week time course. The inflammatory response included a rapid and transient infiltration of granulocytes and Ly6C

conclusionsThese results suggest that iBRB restoration occurs as TJ complexes are reorganized and that resolution of inflammation and restoration of the iBRB following retinal IR injury are functionally linked.

Indexed as

AnimalsApoptosisBlood-Retinal BarrierCapillary PermeabilityDisease Models, AnimalDNA FragmentationInflammationMiceMicrogliaRecovery of FunctionReperfusion InjuryRetinaRetinal VesselsBlood-retina barrierCox-2GranulocytesIL-1βIschemia-reperfusion injuryLeukocytesMicrogliaMinocyclineMonocytesMyeloid-derived macrophagesResolution of inflammationRetinal vasculatureSerpina3nTight junctionsTNF-α

Identifiers

PMID34446062
PMCPMC8394696
OpenAlexW3148037003

What OpenQuestion 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 OpenQuestion graph.