Evidence map›Paper›PMID 32978500›Full record

ArticleScientific reports2020

Myh11+ microvascular mural cells and derived mesenchymal stem cells promote retinal fibrosis.

H Clifton Ray, Bruce A Corliss, Anthony C Bruce, Sam Kesting, Paromita Dey, Jennifer Mansour, Scott A Seaman, Christian M Smolko, Corbin Mathews, Bijan K Dey and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Review
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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

13 authors.

H Clifton Ray *Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Bruce A Corliss *Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Anthony C BruceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Sam KestingDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Paromita DeyThe RNA Institute, University at Albany, State University of New York, Albany, NY, USA.
Jennifer MansourDepartment of Biology, University of Virginia, Charlottesville, VA, USA.
Scott A SeamanDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Christian M SmolkoDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Corbin MathewsDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Bijan K DeyThe RNA Institute, University at Albany, State University of New York, Albany, NY, USA.
Gary K OwensRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
Shayn M PeirceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
Paul A YatesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. pay2x@virginia.edu.

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Adipose Stem Cells for Diabetic RetinopathyR01EY022063 · NEI · UNIVERSITY OF VIRGINIA · PI HERMAN, IRA M, PEIRCE-COTTLER, SHAYN · 2012 to 2015
$2.0M
NEI NIH HHS R01 EY022063NIH HHS EY022063
6 · The paper itself

Abstract

Retinal diseases are frequently characterized by the accumulation of excessive scar tissue found throughout the neural retina. However, the pathophysiology of retinal fibrosis remains poorly understood, and the cell types that contribute to the fibrotic response are incompletely defined. Here, we show that myofibroblast differentiation of mural cells contributes directly to retinal fibrosis. Using lineage tracing technology, we demonstrate that after chemical ocular injury, Myh11+ mural cells detach from the retinal microvasculature and differentiate into myofibroblasts to form an epiretinal membrane. Inhibition of TGFβR attenuates Myh11+ retinal mural cell myofibroblast differentiation, and diminishes the subsequent formation of scar tissue on the surface of the retina. We demonstrate retinal fibrosis within a murine model of oxygen-induced retinopathy resulting from the intravitreal injection of adipose Myh11-derived mesenchymal stem cells, with ensuing myofibroblast differentiation. In this model, inhibiting TGFβR signaling does not significantly alter myofibroblast differentiation and collagen secretion within the retina. This work shows the complexity of retinal fibrosis, where scar formation is regulated both by TGFβR and non-TGFβR dependent processes involving mural cells and derived mesenchymal stem cells. It also offers a cautionary note on the potential deleterious, pro-fibrotic effects of exogenous MSCs once intravitreally injected into clinical patients.

Indexed as

Cell DifferentiationAnimalsCells, CulturedCicatrixFemaleFibrosisMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsMyosin Heavy ChainsRetinal DiseasesSignal Transductionmyosin 11, mouseMyosin Heavy Chains

Identifiers

PMID32978500
PMCPMC7519078

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Registered trials

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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.