Evidence map›Paper›PMID 30098172›Full record

ArticleInvestigative ophthalmology & visual science2018

A Role for βA3/A1-Crystallin in Type 2 EMT of RPE Cells Occurring in Dry Age-Related Macular Degeneration.

Sayan Ghosh, Peng Shang, Hiroto Terasaki, Nadezda Stepicheva, Stacey Hose, Meysam Yazdankhah, Joseph Weiss, Taiji Sakamoto, Imran A Bhutto, Shuli Xia and 5 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
3.8field-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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Review
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  6. Review
  7. Dysregulated DNA Methylation inInternational journal of molecular sciences · 2025
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  8. Article
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  11. Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025
    Article
  12. The RNA content of extracellular vesicles from gene-editedMolecular therapy. Methods & clinical development · 2025
    Article
  13. Article
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  19. Article
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9 more citing papers are in PubMed but not listed here.

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

15 authors at 4 institutions in 2 countries.

Sayan GhoshGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Peng ShangGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Hiroto TerasakiArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
Nadezda StepichevaGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Stacey HoseGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Meysam YazdankhahGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Joseph WeissGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Taiji SakamotoArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
Imran A BhuttoGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Shuli XiaHugo W. Moser Research Institute at Kennedy Krieger and Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
J Samuel ZiglerThe Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Ram KannanArnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, California, United States.
Jiang QianThe Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
James T HandaThe Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Debasish SinhaGlia Research Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
University of Pittsburgh · USJohns Hopkins University · USDoheny Eye Institute · USKagoshima University · JP

Funding

Oxidative stress and innate immunity impair the visual cycleR01EY027691 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2017 to 2021
$2.7M
NEI NIH HHS R01 EY027691
6 · The paper itself

Abstract

Purpose: The RPE cells have a major role in the development of dry age-related macular degeneration (AMD). We present novel evidence that βA3/A1-crystallin, encoded by the Cryba1 gene, a protein known to be important for lysosomal clearance in the RPE, also has a role in epithelial-to-mesenchymal transition (EMT) of RPE cells. Methods: RPE from dry AMD globes, genetically engineered mice lacking Cryba1 globally or specifically in the RPE, spontaneous mutant rats (Nuc1) with a loss-of-function mutation in Cryba1, and the melanoma OCM3 cell line were used. Spatial localization of proteins was demonstrated with immunofluorescence, gene expression levels were determined by quantitative PCR (qPCR), and protein levels by Western blotting. Cell movement was evaluated using wound healing and cell migration assays. Co-immunoprecipitation was used to identify binding partners of βA3/A1-crystallin. Results: βA3/A1-crystallin is upregulated in polarized RPE cells compared to undifferentiated cells. Loss of βA3/A1-crystallin in murine and human RPE cells resulted in upregulation of Snail and vimentin, downregulation of E-cadherin, and increased cell migration. βA3/A1-crystallin binds to cortactin, and loss of βA3/A1-crystallin resulted in increased P-cortactinY421. The RPE from AMD samples had increased Snail and vimentin, and decreased E-cadherin, compared to age-matched controls. Conclusions: We introduced a novel concept of dry AMD initiation induced by lysosomal clearance defects in the RPE and subsequent attempts by RPE cells to avoid the resulting stress by undergoing EMT. We demonstrate that βA3/A1-crystallin is a potential therapeutic target for AMD through rejuvenation of lysosomal dysfunction and potentially, reversal of EMT.

Indexed as

Animalsbeta-Crystallin A ChainBlotting, WesternCell MovementCrystallinsEpithelial-Mesenchymal TransitionGeographic AtrophyHumansImmunohistochemistryMice, KnockoutRatsReal-Time Polymerase Chain ReactionRetinal Pigment EpitheliumRNA, MessengerSnail Family Transcription FactorsTransfectionbetaA3-crystallin, ratbeta-Crystallin A ChainCRYBA1 protein, humanCryba1 protein, mouseCrystallinsRNA, MessengerSnail Family Transcription FactorsVimentin

Identifiers

PMID30098172
PMCPMC6058694
OpenAlexW2887977772

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.