Cargando…

The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early...

Descripción completa

Detalles Bibliográficos
Autores principales: Chidlow, Glyn, Ebneter, Andreas, Wood, John P. M., Casson, Robert J.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098991/
https://www.ncbi.nlm.nih.gov/pubmed/21311901
http://dx.doi.org/10.1007/s00401-011-0807-1
_version_ 1782204021234204672
author Chidlow, Glyn
Ebneter, Andreas
Wood, John P. M.
Casson, Robert J.
author_facet Chidlow, Glyn
Ebneter, Andreas
Wood, John P. M.
Casson, Robert J.
author_sort Chidlow, Glyn
collection PubMed
description The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-011-0807-1) contains supplementary material, which is available to authorized users.
format Text
id pubmed-3098991
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Springer-Verlag
record_format MEDLINE/PubMed
spelling pubmed-30989912011-07-14 The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma Chidlow, Glyn Ebneter, Andreas Wood, John P. M. Casson, Robert J. Acta Neuropathol Original Paper The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-011-0807-1) contains supplementary material, which is available to authorized users. Springer-Verlag 2011-02-11 2011 /pmc/articles/PMC3098991/ /pubmed/21311901 http://dx.doi.org/10.1007/s00401-011-0807-1 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Paper
Chidlow, Glyn
Ebneter, Andreas
Wood, John P. M.
Casson, Robert J.
The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title_full The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title_fullStr The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title_full_unstemmed The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title_short The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
title_sort optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098991/
https://www.ncbi.nlm.nih.gov/pubmed/21311901
http://dx.doi.org/10.1007/s00401-011-0807-1
work_keys_str_mv AT chidlowglyn theopticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT ebneterandreas theopticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT woodjohnpm theopticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT cassonrobertj theopticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT chidlowglyn opticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT ebneterandreas opticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT woodjohnpm opticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma
AT cassonrobertj opticnerveheadisthesiteofaxonaltransportdisruptionaxonalcytoskeletondamageandputativeaxonalregenerationfailureinaratmodelofglaucoma