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Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction

Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However,...

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Autores principales: Sterling, Jacob K., Baumann, Bailey, Foshe, Sierra, Voigt, Andrew, Guttha, Samyuktha, Alnemri, Ahab, McCright, Sam J., Li, Mingyao, Zauhar, Randy J., Montezuma, Sandra R., Kapphahn, Rebecca J., Chavali, Venkata R.M., Hill, David A., Ferrington, Deborah A., Stambolian, Dwight, Mullins, Robert F., Merrick, David, Dunaief, Joshua L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248858/
https://www.ncbi.nlm.nih.gov/pubmed/35705048
http://dx.doi.org/10.1016/j.celrep.2022.110942
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author Sterling, Jacob K.
Baumann, Bailey
Foshe, Sierra
Voigt, Andrew
Guttha, Samyuktha
Alnemri, Ahab
McCright, Sam J.
Li, Mingyao
Zauhar, Randy J.
Montezuma, Sandra R.
Kapphahn, Rebecca J.
Chavali, Venkata R.M.
Hill, David A.
Ferrington, Deborah A.
Stambolian, Dwight
Mullins, Robert F.
Merrick, David
Dunaief, Joshua L.
author_facet Sterling, Jacob K.
Baumann, Bailey
Foshe, Sierra
Voigt, Andrew
Guttha, Samyuktha
Alnemri, Ahab
McCright, Sam J.
Li, Mingyao
Zauhar, Randy J.
Montezuma, Sandra R.
Kapphahn, Rebecca J.
Chavali, Venkata R.M.
Hill, David A.
Ferrington, Deborah A.
Stambolian, Dwight
Mullins, Robert F.
Merrick, David
Dunaief, Joshua L.
author_sort Sterling, Jacob K.
collection PubMed
description Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However, the mechanism of RPE iron accumulation in AMD is unknown. We show that high-fat-diet-induced obesity, a risk factor for AMD, drives systemic and local inflammatory circuits upregulating interleukin-1β (IL-1β). IL-1β upregulates RPE iron importers and downregulates iron exporters, causing iron accumulation, oxidative stress, and dysfunction. We term this maladaptive, chronic activation of a nutritional immunity pathway the cellular iron sequestration response (CISR). RNA sequencing (RNA-seq) analysis of choroid and retina from human donors revealed that hallmarks of this pathway are present in AMD microglia and macrophages. Together, these data suggest that inflamed adipose tissue, through the CISR, can lead to RPE pathology in AMD.
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spelling pubmed-92488582022-07-01 Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction Sterling, Jacob K. Baumann, Bailey Foshe, Sierra Voigt, Andrew Guttha, Samyuktha Alnemri, Ahab McCright, Sam J. Li, Mingyao Zauhar, Randy J. Montezuma, Sandra R. Kapphahn, Rebecca J. Chavali, Venkata R.M. Hill, David A. Ferrington, Deborah A. Stambolian, Dwight Mullins, Robert F. Merrick, David Dunaief, Joshua L. Cell Rep Article Age-related macular degeneration (AMD), the leading cause of irreversible blindness among Americans over 50, is characterized by dysfunction and death of retinal pigment epithelial (RPE) cells. The RPE accumulates iron in AMD, and iron overload triggers RPE cell death in vitro and in vivo. However, the mechanism of RPE iron accumulation in AMD is unknown. We show that high-fat-diet-induced obesity, a risk factor for AMD, drives systemic and local inflammatory circuits upregulating interleukin-1β (IL-1β). IL-1β upregulates RPE iron importers and downregulates iron exporters, causing iron accumulation, oxidative stress, and dysfunction. We term this maladaptive, chronic activation of a nutritional immunity pathway the cellular iron sequestration response (CISR). RNA sequencing (RNA-seq) analysis of choroid and retina from human donors revealed that hallmarks of this pathway are present in AMD microglia and macrophages. Together, these data suggest that inflamed adipose tissue, through the CISR, can lead to RPE pathology in AMD. 2022-06-14 /pmc/articles/PMC9248858/ /pubmed/35705048 http://dx.doi.org/10.1016/j.celrep.2022.110942 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Sterling, Jacob K.
Baumann, Bailey
Foshe, Sierra
Voigt, Andrew
Guttha, Samyuktha
Alnemri, Ahab
McCright, Sam J.
Li, Mingyao
Zauhar, Randy J.
Montezuma, Sandra R.
Kapphahn, Rebecca J.
Chavali, Venkata R.M.
Hill, David A.
Ferrington, Deborah A.
Stambolian, Dwight
Mullins, Robert F.
Merrick, David
Dunaief, Joshua L.
Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title_full Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title_fullStr Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title_full_unstemmed Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title_short Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
title_sort inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248858/
https://www.ncbi.nlm.nih.gov/pubmed/35705048
http://dx.doi.org/10.1016/j.celrep.2022.110942
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