Evidence map›Paper›PMID 26878210›Full record

ArticleThe American journal of pathology2016

αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition.

Keijiro Ishikawa, Parameswaran G Sreekumar, Christine Spee, Hossein Nazari, Danhong Zhu, Ram Kannan, David R Hinton

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 10% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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  17. Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023
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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

7 authors at 2 institutions in 1 country.

Keijiro IshikawaArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Parameswaran G SreekumarArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California.
Christine SpeeDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Hossein NazariDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Danhong ZhuDepartment of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California.
Ram KannanArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California.
David R HintonDepartment of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California; Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California. Electronic address: dhinton@usc.edu.
University of Southern California · USDoheny Eye Institute · 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

Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial-mesenchymal transition (EMT) of retinal pigment epithelium cells. αB-crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of αB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in αB-crystallin knockout mice compared with wild-type mice. αB-crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of αB-crystallin induced EMT, whereas suppression of αB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-β2-induced EMT was further enhanced by overexpression of αB-crystallin but was inhibited by suppression of αB-crystallin. Silencing of αB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 up-regulated αB-crystallin, and its EMT induction was inhibited by knockdown of αB-crystallin. Furthermore, inhibition of αB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of αB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, αB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration.

Indexed as

alpha-Crystallin B ChainAnimalsChoroidal NeovascularizationEpithelial-Mesenchymal TransitionFibronectinsFibrosisHumansMacular DegenerationMaleMice, KnockoutRetinal Pigment Epitheliumalpha-Crystallin B ChainFibronectins

Identifiers

PMID26878210
PMCPMC4822331
OpenAlexW2258772674

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.