ArticleThe Journal of biological chemistry2014
Smoke exposure causes endoplasmic reticulum stress and lipid accumulation in retinal pigment epithelium through oxidative stress and complement activation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- CETP/LPL/LIPC gene polymorphisms and susceptibility to age-related macular degeneration.Scientific reports · 2015Pooled it
- CR2-fH, A Targeted Inhibitor of Alternative Complement Pathway Reduces Dry AMD-Like Phenotype in AMD Patient iPSC-derived RPE Cells.Investigative ophthalmology & visual science · 2026Article
- Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025Article
- Global research trends on endoplasmic reticulum stress in retinal diseases from 2000 to 2024.International ophthalmology · 2025Review
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Complement activation at the interface between adipocytes and cancer cells drives tumor progression.JCI insight · 2025Article
- Impact of smoking on the complement system: a narrative review.Frontiers in immunology · 2025Review
- The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium.Free radical biology & medicine · 2024Article
- Cigarette smoke extract induces ferroptosis in human retinal pigment epithelial cells.Heliyon · 2024Article
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Pigmentation level of human iPSC-derived RPE does not indicate a specific gene expression profile.eLife · 2024Article
- Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.Diagnostics (Basel, Switzerland) · 2024Review
- Dietary sources of antioxidants and oxidative stress in age-related macular degeneration.Frontiers in pharmacology · 2024Article
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease.Tissue engineering and regenerative medicine · 2023Article
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Regulatable Complement Inhibition of the Alternative Pathway Mitigates Wet Age-Related Macular Degeneration Pathology in a Mouse Model.Translational vision science & technology · 2023Article
- Article
- New insight of complement system in the process of vascular calcification.Journal of cellular and molecular medicine · 2023Review
- Evaluating the comorbidities of age and cigarette smoking on stroke outcomes in the context of anti-complement mitigation strategies.Frontiers in immunology · 2023Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD.
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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.