Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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
_version_ 1782154372173529088
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
work_keys_str_mv AT howellgarethr axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT libbyrichardt axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT jakobstatjanac axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT smithrichards axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT phalanfcampbell axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT barterjosephw axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT barbayjessicam axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT marchantjeffreyk axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT maheshnagaraju axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT porciattivittorio axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT whitmorealanv axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT maslandrichardh axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma
AT johnsimonwm axonsofretinalganglioncellsareinsultedintheopticnerveearlyindba2jglaucoma