ArticleCellular microbiology2016
5-Aminoimidazole-4-carboxamide ribonucleoside-mediated adenosine monophosphate-activated protein kinase activation induces protective innate responses in bacterial endophthalmitis.
Article in Cellular microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Myeloid Cell-Specific Deletion of AMPKα1 Worsens Ocular Bacterial Infection by Skewing Macrophage Phenotypes.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.Prostaglandins & other lipid mediators · 2024Review
- Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistantFrontiers in cellular and infection microbiology · 2024Article
- Oral administration of S-nitroso-L-glutathione (GSNO) provides anti-inflammatory and cytoprotective effects during ocular bacterial infections.Cellular and molecular life sciences : CMLS · 2023Article
- Butyrate Ameliorates Intraocular Bacterial Infection by Promoting Autophagy and Attenuating the Inflammatory Response.Infection and immunity · 2023Article
- Article
- Transcriptomics and systems biology identify non-antibiotic drugs for the treatment of ocular bacterial infection.iScience · 2022Article
- Systemic Candida albicans Infection in Mice Causes Endogenous Endophthalmitis via Breaching the Outer Blood-Retinal Barrier.Microbiology spectrum · 2022Article
- Essential Role of NLRP3 Inflammasome in Mediating IL-1β Production and the Pathobiology of Staphylococcus aureus Endophthalmitis.Infection and immunity · 2022Article
- Integrative metabolomics and transcriptomics identifies itaconate as an adjunct therapy to treat ocular bacterial infection.Cell reports. Medicine · 2021Article
- Newly-found functions of metformin for the prevention and treatment of age-related macular degeneration.International journal of ophthalmology · 2021Review
- Bacterial Burden Declines But Neutrophil Infiltration and Ocular Tissue Damage Persist in ExperimentalFrontiers in cellular and infection microbiology · 2021Article
- Transcriptomic and Histological Analysis of Exacerbated Immune Response in Multidrug-ResistantFrontiers in immunology · 2021Article
- Aging, But Not Sex and Genetic Diversity, Impacts the Pathobiology of Bacterial Endophthalmitis.Investigative ophthalmology & visual science · 2020Article
- Toll-like receptor 2 (TLR2) engages endoplasmic reticulum stress sensor IRE1α to regulate retinal innate responses in Staphylococcus aureus endophthalmitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Glycolytic inhibitor 2-deoxyglucose suppresses inflammatory response in innate immune cells and experimental staphylococcal endophthalmitis.Experimental eye research · 2020Article
- Multidrug-ResistantMicroorganisms · 2020Article
- Long non-coding RNA ANRIL alleviates HAging · 2020Article
- Hippo Signaling Pathway Has a Critical Role in Zika Virus Replication and in the Pathogenesis of Neuroinflammation.The American journal of pathology · 2020Article
- AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The retina is considered to be the most metabolically active tissue in the body. However, the link between energy metabolism and retinal inflammation, as incited by microbial infection such as endophthalmitis, remains unexplored. In this study, using a mouse model of Staphylococcus aureus (SA) endophthalmitis, we demonstrate that the activity (phosphorylation) of 5' adenosine monophosphate-activated protein kinase alpha (AMPKα), a cellular energy sensor and its endogenous substrate; acetyl-CoA carboxylase is down-regulated in the SA-infected retina. Intravitreal administration of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), restored AMPKα and acetyl-CoA carboxylase phosphorylation. AICAR treatment reduced both the bacterial burden and intraocular inflammation in SA-infected eyes by inhibiting NF-kB and MAP kinases (p38 and JNK) signalling. The anti-inflammatory effects of AICAR were diminished in eyes pretreated with AMPK inhibitor, Compound C. The bioenergetics (Seahorse) analysis of SA-infected microglia and bone marrow-derived macrophages revealed an increase in glycolysis, which was reinstated by AICAR treatment. AICAR also reduced the expression of SA-induced glycolytic genes, including hexokinase 2 and glucose transporter 1 in microglia, bone marrow-derived macrophages and the mouse retina. Interestingly, AICAR treatment enhanced the bacterial phagocytic and intracellular killing activities of cultured microglia, macrophages and neutrophils. Furthermore, AMPKα1 global knockout mice exhibited increased susceptibility towards SA endophthalmitis, as evidenced by increased inflammatory mediators and bacterial burden and reduced retinal function. Together, these findings provide the first evidence that AMPK activation promotes retinal innate defence in endophthalmitis by modulating energy metabolism and that it can be targeted therapeutically to treat ocular infections.
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Registered trials
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.