ArticleAntioxidants & redox signaling2014
Role of unfolded protein response dysregulation in oxidative injury of retinal pigment epithelial cells.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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
50 citing papers in PubMed, 65 citations in OpenAlex.
- Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD).Biomolecules · 2025Review
- Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey.Investigative ophthalmology & visual science · 2025Article
- TMEM97 governs partial epithelial-mesenchymal transition of retinal pigment epithelial cells via the CTNND2-ADAM10 axis.Molecular therapy. Nucleic acids · 2025Article
- Signaling Pathways in Retinal Pigment Epithelium (RPE) Cells in Response to Stress Conditions of Age-Related Macular Degeneration (AMD).Advances in experimental medicine and biology · 2025Review
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.Cell biochemistry and function · 2024Review
- Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Glycative stress as a cause of macular degeneration.Progress in retinal and eye research · 2024Review
- Transmembrane protein TMEM97 and epigenetic reader BAHCC1 constitute an axis that supports pro-inflammatory cytokine expression.Cellular signalling · 2024Article
- Regulated cell death pathways in the sodium iodate model: Insights and implications for AMD.Experimental eye research · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Essential Role of XBP1 in Maintaining Photoreceptor Synaptic Integrity in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2023Article
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice.Investigative ophthalmology & visual science · 2022Article
- PERK/EIF2AK3 integrates endoplasmic reticulum stress-induced apoptosis, oxidative stress and autophagy responses in immortalised retinal pigment epithelial cells.Scientific reports · 2022Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- Numb-PRRL promotes TGF-β1- and EGF-induced epithelial-to-mesenchymal transition in pancreatic cancer.Cell death & disease · 2022Article
- Article
- Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-κB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium.Antioxidants (Basel, Switzerland) · 2021Article
- TMEM97 ablation aggravates oxidant-induced retinal degeneration.Cellular signalling · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
aimsAge-related macular degeneration (AMD), a major cause of legal blindness in the elderly, is associated with genetic and environmental risk factors, such as cigarette smoking. Recent evidence shows that cigarette smoke (CS) that contains high levels of potent oxidants preferably targets retinal pigment epithelium (RPE) leading to oxidative damage and apoptosis; however, the mechanisms are poorly understood. The present study aimed to investigate the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in CS-related RPE apoptosis.
resultsER stress and proapoptotic gene C/EBP homologous protein (CHOP) were induced in the RPE/choroid complex from mice exposed to CS for 2 weeks and in human RPE cells treated with hydroquinone, a potent oxidant found at high concentrations in CS. Suppressing ER stress or inhibiting CHOP activation by pharmacological chaperones or genetic approaches attenuated hydroquinone-induced RPE cell apoptosis. In contrast to enhanced CHOP activation, protein level of active X-box binding protein 1 (XBP1), a major regulator of the adaptive UPR, was reduced in hydroquinone-treated cells. Conditional knockout of XBP1 gene in the RPE resulted in caspase-12 activation, increased CHOP expression, and decreased antiapoptotic gene Bcl-2. Furthermore, XBP1-deficient RPE cells are more sensitive to oxidative damage induced by hydroquinone or NaIO3, a CS-unrelated chemical oxidant. Conversely, overexpressing XBP1 protected RPE cells and attenuated oxidative stress-induced RPE apoptosis. INNOVATION AND
conclusionThese findings provide strong evidence suggesting an important role of ER stress and the UPR in CS-related oxidative injury of RPE cells. Thus, the modulation of the UPR signaling may provide a promising target for the treatment of AMD.
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Registered trials
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.