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Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma
Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network o...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373494/ https://www.ncbi.nlm.nih.gov/pubmed/18158332 http://dx.doi.org/10.1083/jcb.200706181 |
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author | Howell, Gareth R. Libby, Richard T. Jakobs, Tatjana C. Smith, Richard S. Phalan, F. Campbell Barter, Joseph W. Barbay, Jessica M. Marchant, Jeffrey K. Mahesh, Nagaraju Porciatti, Vittorio Whitmore, Alan V. Masland, Richard H. John, Simon W. M. |
author_facet | Howell, Gareth R. Libby, Richard T. Jakobs, Tatjana C. Smith, Richard S. Phalan, F. Campbell Barter, Joseph W. Barbay, Jessica M. Marchant, Jeffrey K. Mahesh, Nagaraju Porciatti, Vittorio Whitmore, Alan V. Masland, Richard H. John, Simon W. M. |
author_sort | Howell, Gareth R. |
collection | PubMed |
description | Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wld(s) allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve. |
format | Text |
id | pubmed-2373494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-23734942008-06-30 Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma Howell, Gareth R. Libby, Richard T. Jakobs, Tatjana C. Smith, Richard S. Phalan, F. Campbell Barter, Joseph W. Barbay, Jessica M. Marchant, Jeffrey K. Mahesh, Nagaraju Porciatti, Vittorio Whitmore, Alan V. Masland, Richard H. John, Simon W. M. J Cell Biol Research Articles Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wld(s) allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve. The Rockefeller University Press 2007-12-31 /pmc/articles/PMC2373494/ /pubmed/18158332 http://dx.doi.org/10.1083/jcb.200706181 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Howell, Gareth R. Libby, Richard T. Jakobs, Tatjana C. Smith, Richard S. Phalan, F. Campbell Barter, Joseph W. Barbay, Jessica M. Marchant, Jeffrey K. Mahesh, Nagaraju Porciatti, Vittorio Whitmore, Alan V. Masland, Richard H. John, Simon W. M. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title | Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title_full | Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title_fullStr | Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title_full_unstemmed | Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title_short | Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma |
title_sort | axons of retinal ganglion cells are insulted in the optic nerve early in dba/2j glaucoma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373494/ https://www.ncbi.nlm.nih.gov/pubmed/18158332 http://dx.doi.org/10.1083/jcb.200706181 |
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