ArticleProceedings of the National Academy of Sciences of the United States of America2013
Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 87 citations in OpenAlex.
- Mechanistic Insights into Regulation of the Aryl Hydrocarbon Receptor Expression in Mouse and Human Hepatoma Cells.International journal of molecular sciences · 2026Article
- Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.Scientific reports · 2025Article
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.Investigative ophthalmology & visual science · 2025Article
- Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Article
- Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.Neural regeneration research · 2023Review
- An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.Circulation research · 2023Article
- Potential therapeutic targets for age-related macular degeneration: The nuclear option.Progress in retinal and eye research · 2023Review
- CD68: Potential Contributor to Inflammation and RPE Cell Dystrophy.Advances in experimental medicine and biology · 2023Review
- Does senescence play a role in age-related macular degeneration?Experimental eye research · 2022Review
- Characterization and identification of measurable endpoints in a mouse model featuring age-related retinal pathologies: a platform to test therapies.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration.Experimental eye research · 2022Review
- Article
- Gene Delivery of a Caspase Activation and Recruitment Domain Improves Retinal Pigment Epithelial Function and Modulates Inflammation in a Mouse Model with Features of Dry Age-Related Macular Degeneration.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2022Article
- Comparison between sodium iodate and lipid peroxide murine models of age-related macular degeneration for drug evaluation-a narrative review.Annals of eye science · 2022Article
- Osteopontin accumulates in basal deposits of human eyes with age-related macular degeneration and may serve as a biomarker of aging.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease.Frontiers in toxicology · 2022Review
- FLII and MLL1 Cooperatively Regulate Aryl Hydrocarbon Receptor-Mediated Transcription in ARPE-19 Cells.Current issues in molecular biology · 2021Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early dry age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that AhR activity and protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable in AMD, decrease with age. This finding is significant given that age is the most established risk factor for development of AMD. Moreover, AhR(-/-) mice exhibit decreased visual function and develop dry AMD-like pathology, including disrupted RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and linear-like deposit material, Bruch's membrane thickening, and progressive RPE and choroidal atrophy. High-serum low-density lipoprotein levels were also observed in AhR(-/-) mice. In its oxidized form, this lipoprotein can stimulate increased secretion of extracellular matrix molecules commonly found in deposits from RPE cells, in an AhR-dependent manner. This study demonstrates the importance of cellular clearance via the AhR signaling pathway in dry AMD pathogenesis, implicating AhR as a potential target, and the mouse model as a useful platform for validating future therapies.
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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.