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Text
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<a href="http://doi.org/10.1186/s12974-018-1346-7" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/s12974-018-1346-7</a>
Pages
313–313
Issue
1
Volume
15
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Title
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Reduced AMPK activation and increased HCAR activation drive anti-inflammatory response and neuroprotection in glaucoma.
Publisher
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Journal of neuroinflammation
Date
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2018
2018-11
Subject
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AMP-activated protein kinase; AMP-Activated Protein Kinases/*metabolism; Animal; Animals; Biological; Calcium Binding Proteins – Metabolism; Calcium-Binding Proteins/metabolism; Cells – Drug Effects; Cells – Pathology; Diet; Disease Models; Eye Proteins/genetics; Female; G-Protein-Coupled – Metabolism; G-Protein-Coupled/*metabolism; Glaucoma; Glaucoma – Complications; Glaucoma – Pathology; Glaucoma/*complications/pathology; Impact of Events Scale; Inbred DBA; Inflammation – Etiology; Inflammation – Prevention and Control; Inflammation hydroxycarboxylic acid receptor; Inflammation/*etiology/*prevention & control; Ketogenic diet; Ketogenic/methods; Male; Membrane Glycoproteins; Membrane Glycoproteins/genetics; Mice; Microfilament Proteins – Metabolism; Microfilament Proteins/metabolism; Microglia/drug effects/pathology; Models; Mutation; Mutation/genetics; Neuroprotection/drug effects/*physiology; NLR Family; Optic Nerve – Pathology; Optic Nerve/pathology; Phosphotransferases – Metabolism; Proteins; Pyrin Domain-Containing 3 Protein/genetics/metabolism; Receptors; Retina – Drug Effects; Retina – Pathology; Retinal Ganglion Cells/drug effects/*pathology; Transgenic
Creator
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Harun-Or-Rashid Mohammad; Inman Denise M
Description
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BACKGROUND: Glaucoma is a chronic degenerative disease for which inflammation is considered to play a pivotal role in the pathogenesis and progression. In this study, we examined the impact of a ketogenic diet on the inflammation evident in glaucoma as a follow-up to a recent set of experiments in which we determined that a ketogenic diet protected retinal ganglion cell structure and function. METHODS: Both sexes of DBA/2J (D2) mice were placed on a ketogenic diet (keto) or standard rodent chow (untreated) for 8 weeks beginning at 9 months of age. DBA/2J-Gpnmb(+) (D2G) mice were also used as a non-pathological genetic control for the D2 mice. Retina and optic nerve (ON) tissues were micro-dissected and used for the analysis of microglia activation, expression of pro- and anti-inflammatory molecules, and lactate- or ketone-mediated anti-inflammatory signaling. Data were analyzed by immunohistochemistry, quantitative RT-PCR, ELISA, western blot, and capillary tube-based electrophoresis techniques. RESULTS: Microglia activation was observed in D2 retina and ON as documented by intense microglial-specific Iba1 immunolabeling of rounded-up and enlarged microglia. Ketogenic diet treatment reduced Iba1 expression and the activated microglial phenotype. We detected low energy-induced AMP-activated protein kinase (AMPK) phosphorylation in D2 retina and ON that triggered NF-kappaB p65 signaling through its nuclear translocation. NF-kappaB induced pro-inflammatory TNF-alpha,
Identifier
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<a href="http://doi.org/10.1186/s12974-018-1346-7" target="_blank" rel="noreferrer noopener">10.1186/s12974-018-1346-7</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2018
AMP-activated protein kinase
AMP-Activated Protein Kinases/*metabolism
Animal
Animals
Biological
Calcium Binding Proteins – Metabolism
Calcium-Binding Proteins/metabolism
Cells – Drug Effects
Cells – Pathology
Department of Pharmaceutical Sciences
Diet
Disease Models
Eye Proteins/genetics
Female
G-Protein-Coupled – Metabolism
G-Protein-Coupled/*metabolism
Glaucoma
Glaucoma – Complications
Glaucoma – Pathology
Glaucoma/*complications/pathology
Harun-Or-Rashid Mohammad
Impact of Events Scale
Inbred DBA
Inflammation – Etiology
Inflammation – Prevention and Control
Inflammation hydroxycarboxylic acid receptor
Inflammation/*etiology/*prevention & control
Inman Denise M
Journal of neuroinflammation
Ketogenic diet
Ketogenic/methods
Male
Membrane Glycoproteins
Membrane Glycoproteins/genetics
Mice
Microfilament Proteins – Metabolism
Microfilament Proteins/metabolism
Microglia/drug effects/pathology
Models
Mutation
Mutation/genetics
NEOMED College of Pharmacy
Neuroprotection/drug effects/*physiology
NLR Family
Optic Nerve – Pathology
Optic Nerve/pathology
Phosphotransferases – Metabolism
Proteins
Pyrin Domain-Containing 3 Protein/genetics/metabolism
Receptors
Retina – Drug Effects
Retina – Pathology
Retinal Ganglion Cells/drug effects/*pathology
Transgenic