Evidence map›Paper›PMID 28159976›Full record

ArticleInvestigative ophthalmology & visual science2017

Screening and Characterization of Drugs That Protect Corneal Endothelial Cells Against Unfolded Protein Response and Oxidative Stress.

Eun Chul Kim, Tetsuya Toyono, Cynthia A Berlinicke, Donald J Zack, Ula Jurkunas, Tomohiko Usui, Albert S Jun

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 43 citations in OpenAlex.

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  13. Corneal dystrophies.Nature reviews. Disease primers · 2020
    Review
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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 4 institutions in 3 countries.

Eun Chul KimWilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States 2Department of Ophthalmology & Visual Science, Catholic University of Korea, Seoul, Korea.
Tetsuya ToyonoWilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States 3Department of Ophthalmology, University of Tokyo, Tokyo, Japan.
Cynthia A BerlinickeWilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States.
Donald J ZackWilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States 4Departments of Molecular Biology and Genetics, Neuroscience, and Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States.
Ula JurkunasMassachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
Tomohiko UsuiDepartment of Ophthalmology, University of Tokyo, Tokyo, Japan.
Albert S JunWilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States.
Johns Hopkins University · USThe University of Tokyo · JPCatholic University of Korea · KRHarvard University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
A High Content Screening Approach for the Retinal Degenerative DiseasesR01EY024249 · NEI · JOHNS HOPKINS UNIVERSITY · PI BERLINICKE, CYNTHIA · 2015 to 2019
$2.0M
Role of unfolded protein response and COL8A2 in Fuchs corneal dystrophyR01EY019874 · NEI · JOHNS HOPKINS UNIVERSITY · PI JUN, ALBERT S · 2010 to 2014
$2.0M
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY019874NEI NIH HHS R01 EY024249
6 · The paper itself

Abstract

Purpose: To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Methods: Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected "hits" were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs). Results: Forty-one drugs at 20 μM and 55 drugs at 100 μM increased survival of H2O2-challenged cells, and 8 drugs at 20 μM and 2 drugs at 100 μM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H2O2- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (CHOP) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels. Conclusions: Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs' endothelial corneal dystrophy.

Indexed as

8-Hydroxy-2'-DeoxyguanosineAntioxidantsBlotting, WesternCell SurvivalCyclooxygenase InhibitorsDeoxyguanosineDose-Response Relationship, DrugEndoplasmic Reticulum Chaperone BiPEndothelial CellsEndothelium, CornealEnzyme InhibitorsHumansHydrogen PeroxideMefenamic AcidMuscarinic AgonistsOxidative Stress8-Hydroxy-2'-DeoxyguanosineAntioxidantsCyclooxygenase InhibitorsDeoxyguanosineEndoplasmic Reticulum Chaperone BiPEnzyme InhibitorsHSPA5 protein, humanHydrogen PeroxideMefenamic AcidMuscarinic AgonistsOxotremorineThapsigargin

Identifiers

PMID28159976
PMCPMC5295784
OpenAlexW2585270551

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.