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dc.contributor.authorNarayanan, Subhadra P.
dc.contributor.authorSuwanpradid, Jutamas
dc.contributor.authorSaul, Alan
dc.contributor.authorXu, Zhimin
dc.contributor.authorStill, Amber
dc.contributor.authorCaldwell, Robert William
dc.contributor.authorCaldwell, Ruth B.
dc.date.accessioned2012-10-26T20:27:56Z
dc.date.available2012-10-26T20:27:56Z
dc.date.issued2011-07-21en_US
dc.identifier.citationPLoS One. 2011 Jul 21; 6(7):e22460en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21811615en_US
dc.identifier.doi10.1371/journal.pone.0022460en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/751
dc.description.abstractBackground: Retinopathy of prematurity (ROP) is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2) in retinal neuro-glial cell injury in the mouse model of ROP.
dc.description.abstractMethods and Findings: Studies were performed using wild type (WT) and A2 knockout (A2-/-) mice exposed to Oxygen Induced Retinopathy (OIR). Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end) labeling and Western blotting. Electroretinography (ERG) was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the mitochondrial protein Bim were markedly increased in WT OIR retinas compared to controls, whereas the pro-survival mitrochondrial protein BCL-xl was reduced. These alterations were largely blocked in the A2-/- OIR retina.
dc.description.abstractConclusions: Our data implicate A2 in neurodegeneration during ROP. Deletion of A2 significantly improves neuronal survival and function, possibly through the regulation of mitochondrial membrane permeability mediated apoptosis during retinal ischemia. These molecular events are associated with decreased activation of glial cells, suggesting a rescue effect on macroglia as well.
dc.rightsNarayanan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCell Deathen_US
dc.subjectNeuroscienceen_US
dc.subjectSensory Systemsen_US
dc.subjectVisual Systemen_US
dc.subjectMedicineen_US
dc.subjectOphthalmologyen_US
dc.subjectRetinal Disordersen_US
dc.subjectPediatricsen_US
dc.subjectPediatric Ophthalmologyen_US
dc.titleArginase 2 Deletion Reduces Neuro-Glial Injury and Improves Retinal Function in a Model of Retinopathy of Prematurityen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3141070en_US
dc.contributor.corporatenameVascular Biology Center
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy
dc.contributor.corporatenameDepartment of Ophthalmology
dc.contributor.corporatenameDepartment of Pharmacology and Toxicology
refterms.dateFOA2019-04-10T00:46:48Z
html.description.abstractBackground: Retinopathy of prematurity (ROP) is a major cause of vision impairment in low birth weight infants. While previous work has focused on defining the mechanisms of vascular injury leading to retinal neovascularization, recent studies show that neurons are also affected. This study was undertaken to determine the role of the mitochondrial arginine/ornithine regulating enzyme arginase 2 (A2) in retinal neuro-glial cell injury in the mouse model of ROP.
html.description.abstractMethods and Findings: Studies were performed using wild type (WT) and A2 knockout (A2-/-) mice exposed to Oxygen Induced Retinopathy (OIR). Neuronal injury and apoptosis were assessed using immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end) labeling and Western blotting. Electroretinography (ERG) was used to assess retinal function. Neuro-glial injury in WT ROP mice was evident by TUNEL labeling, retinal thinning, decreases in number of rod bipolar cells and glial cell activation as compared with room air controls. Significant reduction in numbers of TUNEL positive cells, inhibition of retinal thinning, preservation of the rod bipolar cells and prevention of glial activation were observed in the A2-/- retinas. Retinal function was markedly impaired in the WT OIR mice as shown by decreases in amplitude of the b-wave of the ERG. This defect was significantly reduced in A2-/- mice. Levels of the pro-apoptotic proteins p53, cleaved caspase 9, cytochrome C and the mitochondrial protein Bim were markedly increased in WT OIR retinas compared to controls, whereas the pro-survival mitrochondrial protein BCL-xl was reduced. These alterations were largely blocked in the A2-/- OIR retina.
html.description.abstractConclusions: Our data implicate A2 in neurodegeneration during ROP. Deletion of A2 significantly improves neuronal survival and function, possibly through the regulation of mitochondrial membrane permeability mediated apoptosis during retinal ischemia. These molecular events are associated with decreased activation of glial cells, suggesting a rescue effect on macroglia as well.


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