ArticleCell reports2022
Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction.
Open access · goldAbstract read
In one paragraph
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
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26citing papers in PubMed, 2 pooled it
3.9field-weighted citation impact, top 6% of its field
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.Neuromolecular medicine · 2025Pooled it
- Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment.Journal of advanced research · 2023Pooled it
- Obesity and Eye Diseases.Nutrients · 2026Review
- CD36-mediated lipid-accumulation in reactive microglia contributes to retinal degeneration via the NLRP3-IL-1β pathway in mice.Nature communications · 2026Article
- Adipocytes influence choroidal neovascularization via PRDM16.EMBO molecular medicine · 2026Article
- Genetic and epidemiological analyses of alcohol consumption patterns and age-related macular degeneration risk among current drinkers: a role for TNFRSF10A.Journal of global health · 2026Article
- Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer.Redox biology · 2026Article
- High glucose diet induces hepatic iron overload contributing to metabolic dysfunction.iScience · 2026Article
- Genome-wide association study reveals genetic architecture and evolution of human retinal pigmentation.Science advances · 2026Article
- The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.Apoptosis : an international journal on programmed cell death · 2025Review
- Utargetome: A targetome prediction tool for modified U1-snRNAs to identify distal-target positions with improved selectivity.PLoS computational biology · 2025Article
- Traditional Chinese Medicine, Ziyin-Mingmu Decoction, Regulates Cholesterol Metabolism, Oxidative Stress, Inflammation and Gut Microbiota in Age-related Macular Degeneration Models.Pharmaceutical research · 2025Article
- Childhood obesity directly increases age-related macular degeneration risk: the role of physiobiological and immune-metabolic function.Journal of global health · 2025Article
- Modified ZhuJing pill protects retinal pigment epithelium against oxidative stress-induced epithelial-mesenchymal transition through Nrf2-mediated Akt/GSK3β pathway.Frontiers in pharmacology · 2025Article
- Modified Zhujing pill regulates RPE cholesterol metabolism and gut microbiota in an age-related macular degeneration mouse model.Frontiers in cellular and infection microbiology · 2025Article
- Elevation of ANXA1 associated with potential protective mechanism against ferroptosis and immune cell infiltration in age-related macular degeneration.European journal of medical research · 2024Article
- Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- Interleukin-17-mediated protective cytokine signaling against degeneration of the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Jacob K SterlingFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Bailey BaumannFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sierra FosheFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Andrew VoigtInstitute for Vision Research, The University of Iowa, Iowa City, IA 52242, USA; Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
Samyuktha GutthaFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Ahab AlnemriFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sam J McCrightMedical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mingyao LiDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Randy J ZauharDepartment of Chemistry & Biochemistry, University of the Sciences, Philadelphia, PA 19104, USA.
Sandra R MontezumaDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Rebecca J KapphahnDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Venkata R M ChavaliFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
David A HillDivision of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Deborah A FerringtonDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Dwight StambolianFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Robert F MullinsInstitute for Vision Research, The University of Iowa, Iowa City, IA 52242, USA; Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
David MerrickDepartment of Medicine, Division of Endocrinology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Joshua L DunaiefFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: jdunaief@pennmedicine.upenn.edu.
Penn Presbyterian Medical Center · USUniversity of Minnesota · USChildren's Hospital of Philadelphia · USUniversity of Iowa · USUniversity of Pennsylvania · USUniversity of the Sciences · US
Funding
Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5MRetinal Iron Transport in Health and DiseaseR01EY015240 · NEI · UNIVERSITY OF PENNSYLVANIA · PI JOSHUA L DUNAIEF · 2004 to 2026
$10.4MGraduate Training in NeuroscienceT32NS105607 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Marc V Fuccillo, Minghong Ma · 2018 to 2026
$5.4MDeconstructing and Modeling the Single Cell Architecture of the Age-Related Macular Degeneration Retina and RPE/ChoroidR01EY031209 · NEI · UNIVERSITY OF PENNSYLVANIA · PI DEANGELIS, MARGARET M, LI, MINGYAO · 2020 to 2024
$2.7MSingle-Cell Transcriptomic Analysis of Human RetinaR01EY030192 · NEI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO · 2019 to 2022
$2.6MThe IL-6 Induced Retinal Iron Sequestration ResponseR01EY028916 · NEI · UNIVERSITY OF PENNSYLVANIA · PI DUNAIEF, JOSHUA L · 2019 to 2023
$2.4MAge-related macular degeneration,mitochondria and the CFH genotypeR01EY026012 · NEI · UNIVERSITY OF MINNESOTA · PI FERRINGTON, DEBORAH ANN · 2016 to 2019
$1.7MStatistical Methods for Single-Cell TranscriptomicsR01GM125301 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, ZHANG, NANCY R · 2017 to 2020
$1.5MIdentification of a mesenchymal progenitor cell hierarchy in adipose tissueK08DK122099 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MERRICK, DAVID MICHAEL · 2019 to 2023
$840kThe role of unique adipose tissue macrophage populations in obesityK08DK116668 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HILL, DAVID ANDREW · 2018 to 2022
$770kIntegrative analysis of bulk and single-cell RNA-seq data from human retina for age-related macular degenerationR21EY031877 · NEI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, XIAO, RUI · 2020 to 2021
$461kDeciphering the role of lipid metabolism pathways in the RPE and their implications for AMDR21EY028273 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CHAVALI, VENKATA RAMANA MURTHY · 2018 to 2019
$443kNEI NIH HHS F30 EY032339NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY015240NEI NIH HHS R01 EY026012NEI NIH HHS R01 EY028916NEI NIH HHS R01 EY030192NEI NIH HHS R01 EY031209NEI NIH HHS R21 EY028273NEI NIH HHS R21 EY031877NIDDK NIH HHS K08 DK116668NIDDK NIH HHS K08 DK122099NIGMS NIH HHS R01 GM125301NINDS NIH HHS T32 NS105607
Abstract
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.
Indexed as
Macular DegenerationRetinal Pigment EpitheliumAdipose TissueHumansIronOxidative StressRetinaIronage-related macular degenerationCP: Immunologyhigh fat dietIL-1βironmacrophagemicroglianeuroinflammationnutritional immunityvisceral adipose
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What Socratic holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
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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 Socratic graph.