Evidence map›Paper›PMID 30154512›Full record

ArticleScientific reports2018

Corneal myofibroblasts inhibit regenerating nerves during wound healing.

Kye-Im Jeon, Holly B Hindman, Tracy Bubel, Thurma McDaniel, Margaret DeMagistris, Christine Callan, Krystel R Huxlin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. 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
5.1field-weighted citation impact, top 5% 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, 57 citations in OpenAlex.

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  12. ACS nano · 2024
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  18. Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023
    Review
  19. Corneal stromal repair and regeneration.Progress in retinal and eye research · 2022
    Review
  20. 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

7 authors at 1 institution in 1 country.

Kye-Im JeonFlaum Eye Institute, University of Rochester, Rochester, NY, USA.ORCID 0000-0002-9180-3014
Holly B HindmanFlaum Eye Institute, University of Rochester, Rochester, NY, USA.
Tracy BubelFlaum Eye Institute, University of Rochester, Rochester, NY, USA.
Thurma McDanielFlaum Eye Institute, University of Rochester, Rochester, NY, USA.
Margaret DeMagistrisFlaum Eye Institute, University of Rochester, Rochester, NY, USA.
Christine CallanFlaum Eye Institute, University of Rochester, Rochester, NY, USA.
Krystel R HuxlinFlaum Eye Institute, University of Rochester, Rochester, NY, USA. huxlin@cvs.rochester.edu.
University of Rochester · US

Funding

VISUAL SCIENCE RESEARCH CTR SUPPORTP30EY001319 · NEI · UNIVERSITY OF ROCHESTER · PI MICHELE RUCCI · 1985 to 2026
$17.5M
The role of PPAR{gamma} ligands in corneal wound healing and opticsR01EY015836 · NEI · UNIVERSITY OF ROCHESTER · PI HUXLIN, KRYSTEL R · 2004 to 2023
$7.1M
NEI NIH HHS P30 EY001319NEI NIH HHS R01 EY015836
6 · The paper itself

Abstract

Abnormal nerve regeneration often follows corneal injury, predisposing patients to pain, dry eye and vision loss. Yet, we lack a mechanistic understanding of this process. A key event in corneal wounds is the differentiation of keratocytes into fibroblasts and scar-forming myofibroblasts. Here, we show for the first time that regenerating nerves avoid corneal regions populated by myofibroblasts in vivo. Recreating this interaction in vitro, we find neurite outgrowth delayed when myofibroblasts but not fibroblasts, are co-cultured with sensory neurons. After neurites elongated sufficiently, contact inhibition was observed with myofibroblasts, but not fibroblasts. Reduced neurite outgrowth in vitro appeared mediated by transforming growth factor beta 1 (TGF-β1) secreted by myofibroblasts, which increased phosphorylation of collapsin response mediating protein 2 (CRMP2) in neurons. The significance of this mechanism was further tested by applying Mitomycin C after photorefractive keratectomy to decrease myofibroblast differentiation. This generated earlier repopulation of the ablation zone by intra-epithelial and sub-basal nerves. Our findings suggest that attaining proper, rapid corneal nerve regeneration after injury may require blocking myofibroblast differentiation and/or TGF-β during wound healing. They also highlight hitherto undefined myofibroblast-neuron signaling processes capable of restricting neurite outgrowth in the cornea and other tissues where scars and nerves co-exist.

Indexed as

CorneaCorneal InjuriesMyofibroblastsNerve RegenerationSensory Receptor CellsWound HealingAnimalsCatsCell DifferentiationEye ProteinsTransforming Growth Factor betaEye ProteinsTransforming Growth Factor beta

Identifiers

PMID30154512
PMCPMC6113331
OpenAlexW2888543494

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.