Evidence map›Paper›PMID 40964715›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Nrf2 Deficiency in Müller Cells Exacerbates Pathological Neovascularization in Ischemic Retinopathy.

Zhenhua Xu, Lingli Zhou, Jie Wang, Hongkwan Cho, Yingxue Cao, Le Shi, Shirley Wu, Yangyiran Xie, Jiang Qian, Elia J Duh

Abstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

3 citing papers in PubMed.

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4 · The record

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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.

Zhenhua XuDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-3854-8616
Lingli ZhouDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-9321-9348
Jie WangDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-7491-7001
Hongkwan ChoDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.
Yingxue CaoDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.
Le ShiDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0009-0004-2751-1174
Shirley WuDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.
Yangyiran XieDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.
Jiang QianDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-0476-3596
Elia J DuhDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-1917-373X

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI JEFFREY MUMM · 1985 to 2026
$22.1M
Sample Processing and Immunoassay Research CoreP30AR070254 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI Antony Rosen · 2016 to 2026
$8.9M
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 EY022683NIAMS NIH HHS P30 AR070254
6 · The paper itself

Abstract

backgroundMüller cells are the major retinal glial cell type and pivotal regulators of pathological neovascularization in ischemic retinopathy. There is great interest in identifying factors that govern Müller cells in vascular regulation. Nrf2 (NF-E2-related factor 2) plays a major protective role in regulating oxidative stress and inflammation. Our group previously discovered that both global and neuroretinal Nrf2 deficiency suppress retinal revascularization and promote pathological neovascularization in a mouse model of oxygen-induced retinopathy. Here, we investigate the cell-intrinsic role of Nrf2 in Müller cells on retinal angiogenesis.

methodsThe role of Müller cell Nrf2 in retinal angiogenesis was investigated in cell culture and the mouse oxygen-induced retinopathy model. Human retinal endothelial cells were cocultured with primary Müller cells transfected with Nrf2 small-interference RNA. Müller cell-specific Nrf2 knockout mice were subjected to oxygen-induced retinopathy. RNA-seq analysis of a Müller cell-specific RiboTag transcriptome was conducted in wild-type and Nrf2-deficient Müller cells.

resultsSilencing Nrf2 in primary Müller cells increased angiogenic activity in retinal endothelial cells. Müller cell-specific Nrf2 deficiency exacerbated pathological neovascularization in oxygen-induced retinopathy, associated with increased Müller cell gliosis and upregulation of retinal Tnfα (tumor necrosis factor alpha). Müller cell Nrf2 deficiency resulted in dysregulation of multiple genes involved in acute-phase response, inflammation, and angiogenesis, including increased expression of

conclusionsNrf2 in Müller cells plays an integral protective role in modulating retinal angiogenesis and inflammatory responses in ischemic retinopathy. Nrf2 is an important regulator of Müller cell state in retinal ischemia and governs the Müller cell transcriptional program, including LCN2, a novel regulator of angiogenesis. This highlights pharmacological activation of Nrf2 as a therapeutic strategy for pathological neovascularization in ischemic retinopathy.

Indexed as

Ependymoglial CellsIschemiaNF-E2-Related Factor 2Retinal NeovascularizationRetinal VesselsAnimalsCells, CulturedCoculture TechniquesDisease Models, AnimalEndothelial CellsHumansMiceMice, Inbred C57BLMice, KnockoutSignal TransductionTumor Necrosis Factor-alphaNFE2L2 protein, humanNfe2l2 protein, mouseNF-E2-Related Factor 2Tumor Necrosis Factor-alphaangiogenesisinflammationneovascularization, pathologicoxygenretinal diseases

Identifiers

PMID40964715
PMCPMC12574687

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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.