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Text
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URL Address
<a href="http://doi.org/10.1371/journal.pone.0065389" target="_blank" rel="noreferrer noopener">http://doi.org/10.1371/journal.pone.0065389</a>
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Pages
17-17
Issue
6
Volume
8
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Title
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Alpha-lipoic Acid Antioxidant Treatment Limits Glaucoma-related Retinal Ganglion Cell Death And Dysfunction
Publisher
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Plos One
Date
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2013
2013-06
Subject
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controlled trial aladin; dba/2j mouse model; glycation end-products; in-vivo; ischemia-reperfusion; nitric-oxide; open-angle glaucoma; optic neuropathy; oxidative stress; Science & Technology - Other Topics; trabecular meshwork
Creator
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Inman D M; Lambert W S; Calkins D J; Horner P J
Description
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Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense of long-term testing, few studies have modeled antioxidant therapy for prevention of neurodegeneration. We investigated the contribution of oxidative stress to the pathogenesis of glaucoma in the DBA/2J mouse model of glaucoma. Similar to other neurodegenerative diseases, we observed lipid peroxidation and upregulation of oxidative stress-related mRNA and protein in DBA/2J retina. To test the role of oxidative stress in disease progression, we chose to deliver the naturally occurring, antioxidant alpha-lipoic acid (ALA) to DBA/2J mice in their diet. We used two paradigms for ALA delivery: an intervention paradigm in which DBA/2J mice at 6 months of age received ALA in order to intervene in glaucoma development, and a prevention paradigm in which DBA/2J mice were raised on a diet supplemented with ALA, with the goal of preventing glaucoma development. At 10 and 12 months of age (after 4 and 11 months of dietary ALA respectively), we measured changes in genes and proteins related to oxidative stress, retinal ganglion cell (RGC) number, axon transport, and axon number and integrity. Both ALA treatment paradigms showed increased antioxidant gene and protein expression, increased protection of RGCs and improved retrograde transport compared to control. Measures of lipid peroxidation, protein nitrosylation, and DNA oxidation in retina verified decreased oxidative stress in the prevention and intervention paradigms. These data demonstrate the utility of dietary therapy for reducing oxidative stress and improving RGC survival in glaucoma.
Identifier
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<a href="http://doi.org/10.1371/journal.pone.0065389" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0065389</a>
Format
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Journal Article or Conference Abstract Publication
2013
Calkins D J
controlled trial aladin
dba/2j mouse model
Department of Pharmaceutical Sciences
glycation end-products
Horner P J
in-vivo
Inman D M
ischemia-reperfusion
Journal Article or Conference Abstract Publication
Lambert W S
NEOMED College of Pharmacy
nitric-oxide
open-angle glaucoma
optic neuropathy
Oxidative Stress
PloS one
Science & Technology - Other Topics
trabecular meshwork