Evidence map›Paper›PMID 32179077›Full record

ArticleExperimental eye research2020

Dasatinib inhibits peripapillary scleral myofibroblast differentiation.

Amanda Chow, Liam McCrea, Elizabeth Kimball, Julie Schaub, Harry Quigley, Ian Pitha

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental eye research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Amanda ChowDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Liam McCreaDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Elizabeth KimballGlaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Julie SchaubGlaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Harry QuigleyDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Center for Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Glaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Ian PithaDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Center for Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Glaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: ipitha1@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Donald J. Zack · 1985 to 2026
$22.1M
PATHOGENESIS OF GLAUCOMATOUS OPTIC NERVE DAMAGER01EY002120 · NEI · JOHNS HOPKINS UNIVERSITY · PI QUIGLEY, HARRY ALAN · 1985 to 2025
$12.6M
Strategies to achieve sustained medication delivery in glaucoma treatmentK08EY024952 · NEI · JOHNS HOPKINS UNIVERSITY · PI PITHA, IAN FRANZ · 2015 to 2019
$957k
Pathogenesis of Glaucomatous Optic Nerve DamageR56EY002120 · NEI · JOHNS HOPKINS UNIVERSITY · PI QUIGLEY, HARRY ALAN · 2008 to 2008
$369k
NEI NIH HHS K08 EY024952NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY002120NEI NIH HHS R56 EY002120
6 · The paper itself

Abstract

Scleral fibroblast activation occurs in glaucomatous and myopic eyes. Here we perform an unbiased screen to identify kinase inhibitors that reduce fibroblast activation to diverse stimuli in vitro and to in vivo intraocular pressure (IOP) elevation. Primary cultures of peripapillary scleral (PPS) fibroblasts from two human donors were screened using a library of 80 kinase inhibitors to identify compounds that inhibit TGFβ-induced extracellular matrix (ECM) synthesis. Inhibition of myofibroblast differentiation was verified by alpha smooth muscle actin (αSMA) immunoblot and collagen contraction assay. Inhibition of IOP-induced scleral fibroblast proliferation was assessed by ELISA assay for proliferating cell nuclear antigen (PCNA). The initial screen identified 7 inhibitors as showing>80% reduction in ECM binding. Three kinase inhibitors were verified to reduce TGFβ-induced αSMA expression and cellular contractility (rottlerin, PP2, tyrphostin 9). The effect of three Src inhibitors, bosutinib, dasatinib, and SU-6656, on myofibroblast differentiation was evaluated, with only dasatinib significantly inhibiting TGFβ-induced ECM synthesis, αSMA expression, and cellular contractility at nanomolar dosages. Subconjunctival injection of dasatinib reduced IOP-induced scleral fibroblast proliferation compared to control (4.9 ± 11.1 ng/sclera with 0.1 μM versus 88.7 ± 38.6 ng/sclera in control, P < 0.0001). Dasatinib inhibits scleral myofibroblast differentiation and there is pharmacologic evidence that this inhibition is not solely due to Src-kinase inhibition.

Indexed as

AgedAged, 80 and overAnimalsCell DifferentiationCells, CulturedDasatinibDisease Models, AnimalFemaleGlaucomaHumansMaleMiceMyofibroblastsProtein Kinase InhibitorsScleraSignal TransductionDasatinibProtein Kinase InhibitorsFibroblastFibrosisGlaucomaKinase inhibitorPeripapillary scleraScleral remodelingSrc kinase

Identifiers

PMID32179077
PMCPMC7217736
OpenAlexW3011987904

What OpenQuestion holds

Textmetadata
LicenceTDM
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.