Evidence map›Paper›PMID 31669760›Full record

ArticleFree radical biology & medicine2020

Inhibition of the Keap1-Nrf2 protein-protein interaction protects retinal cells and ameliorates retinal ischemia-reperfusion injury.

Qiaoyan Hui, Marcus Karlstetter, Zhenhua Xu, Jing Yang, Lingli Zhou, Hanna M Eilken, Carsten Terjung, Hongkwan Cho, Junsong Gong, Michael J Lai and 2 more

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

Article in Free radical biology & medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. Article
  3. Autophagy: a double-edged sword in ischemia-reperfusion injury.Cellular & molecular biology letters · 2025
    Review
  4. Review
  5. Article
  6. RARRES1 attenuates HFrontiers in physiology · 2025
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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

12 authors at 4 institutions in 3 countries.

Qiaoyan HuiDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Marcus KarlstetterBayer AG, Wuppertal, Germany.
Zhenhua XuDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jing YangDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Lingli ZhouDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hanna M EilkenBayer AG, Wuppertal, Germany.
Carsten TerjungBayer AG, Wuppertal, Germany.
Hongkwan ChoDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Junsong GongDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael J LaiDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Khaled NassarBayer AG, Wuppertal, Germany. Electronic address: khaled.nassar@bayer.com.
Elia J DuhDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: eduh@jhmi.edu.
Bayer (Germany) · DEJohns Hopkins University · USJohns Hopkins Medicine · USFirst Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Malia Michelle Edwards · 1985 to 2026
$22.1M
Regulation of diabetic retinopathy by Nrf2R01EY022383 · NEI · JOHNS HOPKINS UNIVERSITY · PI DUH, ELIA J · 2012 to 2020
$3.8M
Role of Nrf2 in retinal vascularization and ROPR01EY022683 · NEI · JOHNS HOPKINS UNIVERSITY · PI DUH, ELIA J · 2012 to 2021
$3.6M
NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY022383NEI NIH HHS R01 EY022683
6 · The paper itself

Abstract

The Nrf2-Keap1 pathway regulates transcription of a wide array of antioxidant and cytoprotective genes and offers critical protection against oxidative stress. This pathway has demonstrated benefit for a variety of retinal conditions. Retinal ischemia plays a pivotal role in many vision threatening diseases. Retinal vascular endothelial cells are an important participant in ischemic injury. In this setting, Nrf2 provides a protective pathway via amelioration of oxidative stress and inflammation. In this study, we investigated a potent small molecule inhibitor of the Nrf2-Keap1 protein-protein interaction (PPI), CPUY192018, for its therapeutic potential in retinal cells and retinal ischemia-reperfusion injury. In human retinal endothelial cells (HREC), treatment with CPUY192018 increased Nrf2 protein levels and nuclear translocation, stimulated Nrf2-ARE-induced transcriptional capacity, and induced Nrf2 target gene expression. Furthermore, CPUY192018 protected HREC against oxidative stress and inflammatory activation. CPUY192018 also activated Nrf2 and suppressed inflammatory response in macrophages. In the retinal ischemia-reperfusion (I/R) model, administration of CPUY192018 induced Nrf2 target gene activation in the retina. Both systemic and topical treatment with CPUY192018 rescued visual function after ischemia-reperfusion injury. Taken together, these findings indicate that small molecule Keap1-Nrf2 PPI inhibitors can activate the Nrf2 pathway in the retina and provide protection against retinal ischemic and inflammatory injury, suggesting Keap1-Nrf2 PPI inhibition in the treatment of retinal conditions.

Indexed as

NF-E2-Related Factor 2Reperfusion InjuryEndothelial CellsHumansKelch-Like ECH-Associated Protein 1Oxidative StressRetinaKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Endothelial cellInflammationIschemiaNrf2Oxidative stressRetina

Identifiers

PMID31669760
PMCPMC6942228
OpenAlexW2986733785

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.