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More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor originally identified as an environmental sensor of xenobiotic chemicals. However, studies have revealed that the AHR regulates crucial aspects of cell growth and metabolism, development and the immune system. The importa...

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Autores principales: Hammond, Christine L., Roztocil, Elisa, Gupta, Vardaan, Feldon, Steven E., Woeller, Collynn F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915869/
https://www.ncbi.nlm.nih.gov/pubmed/35295218
http://dx.doi.org/10.3389/ftox.2022.791082
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author Hammond, Christine L.
Roztocil, Elisa
Gupta, Vardaan
Feldon, Steven E.
Woeller, Collynn F.
author_facet Hammond, Christine L.
Roztocil, Elisa
Gupta, Vardaan
Feldon, Steven E.
Woeller, Collynn F.
author_sort Hammond, Christine L.
collection PubMed
description The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor originally identified as an environmental sensor of xenobiotic chemicals. However, studies have revealed that the AHR regulates crucial aspects of cell growth and metabolism, development and the immune system. The importance of the AHR and AHR signaling in eye development, toxicology and disease is now being uncovered. The AHR is expressed in many ocular tissues including the retina, choroid, cornea and the orbit. A significant role for the AHR in age-related macular degeneration (AMD), autoimmune uveitis, and other ocular diseases has been identified. Ligands for the AHR are structurally diverse organic molecules from exogenous and endogenous sources. Natural AHR ligands include metabolites of tryptophan and byproducts of the microbiome. Xenobiotic AHR ligands include persistent environmental pollutants such as dioxins, benzo (a) pyrene [B (a) P] and polychlorinated biphenyls (PCBs). Pharmaceutical agents including the proton pump inhibitors, esomeprazole and lansoprazole, and the immunosuppressive drug, leflunomide, activate the AHR. In this review, we highlight the role of the AHR in the eye and discuss how AHR signaling is involved in responding to endogenous and environmental stimuli. We also present the emerging concept that the AHR is a promising therapeutic target for eye disease.
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spelling pubmed-89158692022-03-15 More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease Hammond, Christine L. Roztocil, Elisa Gupta, Vardaan Feldon, Steven E. Woeller, Collynn F. Front Toxicol Toxicology The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor originally identified as an environmental sensor of xenobiotic chemicals. However, studies have revealed that the AHR regulates crucial aspects of cell growth and metabolism, development and the immune system. The importance of the AHR and AHR signaling in eye development, toxicology and disease is now being uncovered. The AHR is expressed in many ocular tissues including the retina, choroid, cornea and the orbit. A significant role for the AHR in age-related macular degeneration (AMD), autoimmune uveitis, and other ocular diseases has been identified. Ligands for the AHR are structurally diverse organic molecules from exogenous and endogenous sources. Natural AHR ligands include metabolites of tryptophan and byproducts of the microbiome. Xenobiotic AHR ligands include persistent environmental pollutants such as dioxins, benzo (a) pyrene [B (a) P] and polychlorinated biphenyls (PCBs). Pharmaceutical agents including the proton pump inhibitors, esomeprazole and lansoprazole, and the immunosuppressive drug, leflunomide, activate the AHR. In this review, we highlight the role of the AHR in the eye and discuss how AHR signaling is involved in responding to endogenous and environmental stimuli. We also present the emerging concept that the AHR is a promising therapeutic target for eye disease. Frontiers Media S.A. 2022-03-03 /pmc/articles/PMC8915869/ /pubmed/35295218 http://dx.doi.org/10.3389/ftox.2022.791082 Text en Copyright © 2022 Hammond, Roztocil, Gupta, Feldon and Woeller. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Toxicology
Hammond, Christine L.
Roztocil, Elisa
Gupta, Vardaan
Feldon, Steven E.
Woeller, Collynn F.
More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title_full More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title_fullStr More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title_full_unstemmed More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title_short More than Meets the Eye: The Aryl Hydrocarbon Receptor is an Environmental Sensor, Physiological Regulator and a Therapeutic Target in Ocular Disease
title_sort more than meets the eye: the aryl hydrocarbon receptor is an environmental sensor, physiological regulator and a therapeutic target in ocular disease
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915869/
https://www.ncbi.nlm.nih.gov/pubmed/35295218
http://dx.doi.org/10.3389/ftox.2022.791082
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