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URL Address
<a href="http://doi.org/10.1167/iovs.14-16126" target="_blank" rel="noreferrer noopener">http://doi.org/10.1167/iovs.14-16126</a>
Pages
1437–1446
Issue
3
Volume
56
Dublin Core
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Title
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Mitochondrial morphology differences and mitophagy deficit in murine glaucomatous optic nerve.
Publisher
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Investigative ophthalmology & visual science
Date
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2015
2015-02
Subject
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*Disease Models; Adenosine Triphosphate/metabolism; Age Factors; Animal; Animals; autophagosome; Axons/pathology; Electron; Inbred DBA; Mice; Microscopy; mitochondria; Mitochondria/*pathology; Mitochondrial Degradation/*physiology; mitophagy; Myelinated/pathology; Nerve Fibers; Optic Nerve/*pathology
Creator
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Coughlin Lucy; Morrison Richard S; Horner Philip J; Inman Denise M
Description
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PURPOSE: Decreased ATP correlates with intraocular pressure exposure in the optic nerves of mice with glaucoma. To understand what underlies this energy deficit, we examined mitochondria in the myelinated optic nerve axons of the DBA/2J mouse, a model of glaucoma secondary to iris pigment disease, and the DBA/2(wt-gpnmb) control strain. METHODS: Mitochondrial length, width, surface area, and health status were measured in 30 electron microscopic fields within the myelinated portion of optic nerves from DBA/2J and DBA/2(wt-gpnmb) mice at 3, 6, and 10 months of age. Protein was isolated from optic nerve for analysis of PINK1, Parkin, LC3-I and -II, and lysosome-associated membrane protein 1 (LAMP1) by Western blot. RESULTS: The number of mitochondria in DBA/2J optic nerve was increased, and they had significantly smaller surface area. Mitochondria in DBA/2J were closer to the axolemma, more spatially isolated, and their cristae were more disrupted at every age group as compared to DBA/2(wt-gpnmb). Autophagosomes were significantly increased in DBA/2J optic nerve at all ages. Protein analysis showed higher LC3-II to LC3-I ratio in aged DBA/2J optic nerve than in DBA/2(wt-gpnmb). PINK1 and Parkin levels were not statistically different across age groups. LAMP1 was significantly decreased in the aged DBA/2J optic nerve. CONCLUSIONS: Decreased surface area, combined with reduced oxidative capacity in mitochondria from the aged DBA/2J axon, indicate that mitochondrial pathology may contribute to the energy deficit in glaucomatous optic nerve. Though autophagosomes were increased in DBA/2J optic nerve, the increased mitochondria and decreased LAMP1 suggest deteriorating mitochondria are not being efficiently recycled by mitophagy.
Identifier
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<a href="http://doi.org/10.1167/iovs.14-16126" target="_blank" rel="noreferrer noopener">10.1167/iovs.14-16126</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).
*Disease Models
2015
Adenosine Triphosphate/metabolism
Age Factors
Animal
Animals
autophagosome
Axons/pathology
Coughlin Lucy
Department of Pharmaceutical Sciences
Electron
Horner Philip J
Inbred DBA
Inman Denise M
Investigative ophthalmology & visual science
Mice
Microscopy
Mitochondria
Mitochondria/*pathology
Mitochondrial Degradation/*physiology
mitophagy
Morrison Richard S
Myelinated/pathology
NEOMED College of Pharmacy
Nerve Fibers
Optic Nerve/*pathology