| Reduced nitro-oxidative stress and neural cell death suggests a protective role for microglial cells in TNFalpha-/- mice in ischemic retinopathy. | |
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MedLine Citation:
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PMID: 20107169 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Neovascularization occurs in response to tissue ischemia and growth factor stimulation. In ischemic retinopathies, however, new vessels fail to restore the hypoxic tissue; instead, they infiltrate the transparent vitreous. In a model of oxygen-induced retinopathy (OIR), TNFalpha and iNOS, upregulated in response to tissue ischemia, are cytotoxic and inhibit vascular repair. The aim of this study was to investigate the mechanism for this effect. METHODS: Wild-type C57/BL6 (WT) and TNFalpha(-/-) mice were subjected to OIR by exposure to 75% oxygen (postnatal days 7-12). The retinas were removed during the hypoxic phase of the model. Retinal cell death was determined by TUNEL staining, and the microglial cells were quantified after Z-series capture with a confocal microscope. In situ peroxynitrite and superoxide were measured by using the fluorescent dyes DCF and DHE. iNOS, nitrotyrosine, and arginase were analyzed by real-time PCR, Western blot analysis, and activity determined by radiolabeled arginine conversion. Astrocyte coverage was examined after GFAP immunostaining. RESULTS: The TNFalpha(-/-) animals displayed a significant reduction in TUNEL-positive apoptotic cells in the inner nuclear layer of the avascular retina compared with that in the WT control mice. The reduction coincided with enhanced astrocytic survival and an increase in microglial cells actively engaged in phagocytosing apoptotic debris that displayed low ROS, RNS, and NO production and high arginase activity. CONCLUSIONS: Collectively, the results suggest that improved vascular recovery in the absence of TNFalpha is associated with enhanced astrocyte survival and that both phenomena are dependent on preservation of microglial cells that display an anti-inflammatory phenotype during the early ischemic phase of OIR. |
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Authors:
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Laura Stevenson; Nuria Matesanz; Liza Colhoun; Kevin Edgar; Adrian Devine; Tom A Gardiner; Denise M McDonald |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-27 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 51 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-11 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 3291-9 Citation Subset: IM |
Affiliation:
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Centre for Vision and Vascular Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Arginase / metabolism Blotting, Western Cell Count Cell Death Cell Survival In Situ Nick-End Labeling Ischemia / metabolism*, pathology Mice Mice, Inbred C57BL Mice, Knockout Microglia / cytology* Nitric Oxide Synthase Type II / metabolism Nitrosation Oxidative Stress* Oxygen / toxicity Reactive Nitrogen Species / metabolism Reactive Oxygen Species / metabolism Retinal Diseases / metabolism*, pathology Retinal Neurons / pathology* Retinal Vessels / metabolism* Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha / physiology* Tyrosine / analogs & derivatives, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 7782-44-7/Oxygen; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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