1
40
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
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
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Mitochondrial morphology differences and mitophagy deficit in murine glaucomatous optic nerve.
Publisher
An entity responsible for making the resource available
Investigative ophthalmology & visual science
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-02
Subject
The topic of the resource
*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
An entity primarily responsible for making the resource
Coughlin Lucy; Morrison Richard S; Horner Philip J; Inman Denise M
Description
An account of the resource
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>
Rights
Information about rights held in and over the resource
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
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.exer.2015.11.016" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.exer.2015.11.016</a>
Pages
22–33
Volume
150
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Early astrocyte redistribution in the optic nerve precedes axonopathy in the DBA/2J mouse model of glaucoma.
Publisher
An entity responsible for making the resource available
Experimental eye research
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-09
Subject
The topic of the resource
*Astrocyte; *Axonopathy; *Glaucoma; *Gliosis; *Neurodegeneration; *Retinal ganglion cell; Animal; Animals; Astrocytes/*pathology; Axons/pathology; Disease Models; Glaucoma; Imaging; Inbred DBA; Mice; Nerve Degeneration/etiology/*pathology; Open-Angle/*pathology; Optic Nerve Diseases/etiology/*pathology; Optic Nerve/*pathology; Photomicrography; Retinal Ganglion Cells/*pathology; Three-Dimensional; Time Factors
Creator
An entity primarily responsible for making the resource
Cooper Melissa L; Crish Samuel D; Inman Denise M; Horner Philip J; Calkins David J
Description
An account of the resource
Glaucoma challenges the survival of retinal ganglion cell axons in the optic nerve through processes dependent on both aging and ocular pressure. Relevant stressors likely include complex interplay between axons and astrocytes, both in the retina and optic nerve. In the DBA/2J mouse model of pigmentary glaucoma, early progression involves axonopathy characterized by loss of functional transport prior to outright degeneration. Here we describe novel features of early pathogenesis in the DBA/2J nerve. With age the cross-sectional area of the nerve increases; this is associated generally with diminished axon packing density and survival and increased glial coverage of the nerve. However, for nerves with the highest axon density, as the nerve expands mean cross-sectional axon area enlarges as well. This early expansion was marked by disorganized axoplasm and accumulation of hyperphosphorylated neurofilamants indicative of axonopathy. Axon expansion occurs without loss up to a critical threshold for size (about 0.45-0.50 mum(2)), above which additional expansion tightly correlates with frank loss of axons. As well, early axon expansion prior to degeneration is concurrent with decreased astrocyte ramification with redistribution of processes towards the nerve edge. As axons expand beyond the critical threshold for loss, glial area resumes an even distribution from the center to edge of the nerve. We also found that early axon expansion is accompanied by reduced numbers of mitochondria per unit area in the nerve. Finally, our data indicate that both IOP and nerve expansion are associated with axon enlargement and reduced axon density for aged nerves. Collectively, our data support the hypothesis that diminished bioenergetic resources in conjunction with early nerve and glial remodeling could be a primary inducer of progression of axon pathology in glaucoma.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.exer.2015.11.016" target="_blank" rel="noreferrer noopener">10.1016/j.exer.2015.11.016</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Astrocyte
*Axonopathy
*Glaucoma
*Gliosis
*neurodegeneration
*Retinal ganglion cell
2016
Animal
Animals
Astrocytes/*pathology
Axons/pathology
Calkins David J
Cooper Melissa L
Crish Samuel D
Department of Pharmaceutical Sciences
Disease Models
Experimental eye research
Glaucoma
Horner Philip J
Imaging
Inbred DBA
Inman Denise M
Mice
NEOMED College of Pharmacy
Nerve Degeneration/etiology/*pathology
Open-Angle/*pathology
Optic Nerve Diseases/etiology/*pathology
Optic Nerve/*pathology
Photomicrography
Retinal Ganglion Cells/*pathology
Three-Dimensional
Time Factors