ArticleInvestigative ophthalmology & visual science2022
Dependence of Retinal Pigment Epithelium Integrity on the NRF2-Heme Oxygenase-1 Axis.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Effects of HO-1 on the Integrity of Retinal Pigment Epithelial Cells in Regulating Axial Elongation in Experimental Myopia.Investigative ophthalmology & visual science · 2026Article
- Curcuma longa-derived extracellular vesicle-like particles ameliorate retinal neovascularization through HIF-1α and NRF2 signaling.Journal of nanobiotechnology · 2026Article
- A Cross-Species Hydroquinone Model Replicates Smoking-Related Corneal Endothelial Oxidative Injury and Enables Therapeutic Screening of FGF10.Investigative ophthalmology & visual science · 2026Article
- Retinal Pigment Epithelium and Monocytes' Mitochondrial Control of Ferroptosis and its Relevance to Age-Related Macular Degeneration.Molecular neurobiology · 2025Article
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Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Purpose: Tight junctions (TJs) form the structural basis of retinal pigment epithelium (RPE) barrier functions. Although oxidative stress contributes to age-related macular degeneration, it is unclear how RPE TJ integrity is controlled by redox balance. In this study, we investigated the protective roles of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor, and heme oxygenase-1 (HO1), a heme-degrading enzyme encoded by the NRF2 target gene HMOX1. Methods: ARPE19 cell cultures and mice, including wild-type, Nrf2-/-, and RPE-specific NRF2-deficient mice, were treated with chemicals that impose oxidative stress or impact heme metabolism. In addition, NRF2 and HO1 expression in ARPE19 cells was knocked down by siRNA. TJ integrity was examined by anti-zonula occludens-1 staining of cultured cells or flatmount RPE tissues from mice. RPE barrier functions were evaluated by transepithelium electrical resistance in ARPE19 cells and immunofluorescence staining for albumin or dextran in eye histological sections. Results: TJ structures and RPE barrier functions were compromised due to oxidant exposure and NRF2 deficiency but were rescued by HO1 inducer. Furthermore, treatment with HO1 inhibitor or heme precursor is destructive to TJ structures and RPE barrier properties. Interestingly, both NRF2 and HO1 were upregulated under oxidative stress, probably as an adaptive response to mitigate oxidant-inflicted damages. Conclusions: Our data indicate that the NRF2-HO1 axis protects TJ integrity and RPE barrier functions by driving heme degradation.
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Registered trials
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