Evidence map›Paper›PMID 26305530›Full record

ArticleInvestigative ophthalmology & visual science2015

Inhibition of DNA Methylation and Methyl-CpG-Binding Protein 2 Suppresses RPE Transdifferentiation: Relevance to Proliferative Vitreoretinopathy.

Shikun He, Ernesto Barron, Keijiro Ishikawa, Hossein Nazari Khanamiri, Chris Spee, Peng Zhou, Satoru Kase, Zhuoshi Wang, Laurie Diane Dustin, David R Hinton

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Dysregulated DNA Methylation inInternational journal of molecular sciences · 2025
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  14. DNA Methylation Contributes to the Differential Expression Levels ofInternational journal of molecular sciences · 2019
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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

10 authors at 2 institutions in 1 country.

Shikun HeDepartment of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 2Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, Unit.
Ernesto BarronDoheny Eye Institute, Los Angeles, California, United States.
Keijiro IshikawaDoheny Eye Institute, Los Angeles, California, United States.
Hossein Nazari KhanamiriDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
Chris SpeeDepartment of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
Peng ZhouDoheny Eye Institute, Los Angeles, California, United States.
Satoru KaseDoheny Eye Institute, Los Angeles, California, United States.
Zhuoshi WangDoheny Eye Institute, Los Angeles, California, United States.
Laurie Diane DustinDepartment of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
David R HintonDepartment of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 2Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, Unit.
Doheny Eye Institute · USUniversity of Southern California · US

Funding

VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
EXPERIMENTAL APPROACH TO MACULOPATHYR01EY001545 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HINTON, DAVID R. · 1985 to 2016
$6.0M
NEI NIH HHS EY01545NEI NIH HHS EY03040NEI NIH HHS P30 EY003040NEI NIH HHS R01 EY001545
6 · The paper itself

Abstract

purposeThe purpose of this study was to evaluate expression of methyl-CpG-binding protein 2 (MeCP2) in epiretinal membranes from patients with proliferative vitreoretinopathy (PVR) and to investigate effects of inhibition of MeCP2 and DNA methylation on transforming growth factor (TGF)-β-induced retinal pigment epithelial (RPE) cell transdifferentiation.

methodsExpression of MeCP2 and its colocalization with cytokeratin and α-smooth muscle actin (α-SMA) in surgically excised PVR membranes was studied using immunohistochemistry. The effects of 5-AZA-2'-deoxycytidine (5-AZA-dC) on human RPE cell migration and viability were evaluated using a modified Boyden chamber assay and the colorimetric 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Expression of RASAL1 mRNA and its promoter region methylation were evaluated by real-time PCR and methylation-specific PCR. Effects of 5-AZA-dC on expression of α-SMA, fibronectin (FN), and TGF-β receptor 2 (TGF-β R2) and Smad2/3 phosphorylation were analyzed by Western blotting. Effect of short interfering RNA (siRNA) knock-down of MeCP2 on expression of α-SMA and FN induced by TGFβ was determined.

resultsMeCP2 was abundantly expressed in cells within PVR membranes where it was double labeled with cells positive for cytokeratin and α-SMA. 5-AZA-dC inhibited expression of MeCP2 and suppressed RASAL1 gene methylation while increasing expression of the RASAL1 gene. Treatment with 5-AZA-dC significantly suppressed the expression of α-SMA, FN, TGF-β R2 and phosphorylation of Smad2/3 and inhibited RPE cell migration. TGF-β induced expression of α-SMA, and FN was suppressed by knock-down of MeCP2.

conclusionsMeCP2 and DNA methylation regulate RPE transdifferentiation and may be involved in the pathogenesis of PVR.

Indexed as

Gene Expression RegulationAzacitidineBlotting, WesternCell MovementCells, CulturedCell TransdifferentiationDecitabineDNADNA MethylationDNA Modification MethylasesEnzyme InhibitorsEpithelial-Mesenchymal TransitionHumansImmunohistochemistryMethyl-CpG-Binding Protein 2PhosphorylationAzacitidineDecitabineDNADNA Modification MethylasesEnzyme InhibitorsMethyl-CpG-Binding Protein 2

Identifiers

PMID26305530
PMCPMC4553933
OpenAlexW1901220621

What OpenQuestion holds

Textmetadata
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.