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
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Open Access
- 11 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Acta Neuropathologica
- Vol. 121 (6), 737-751
- https://doi.org/10.1007/s00401-011-0807-1
Abstract
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.Keywords
This publication has 46 references indexed in Scilit:
- Distal axonopathy with structural persistence in glaucomatous neurodegenerationProceedings of the National Academy of Sciences of the United States of America, 2010
- Ocular hypertension impairs optic nerve axonal transport leading to progressive retinal ganglion cell degenerationExperimental Eye Research, 2010
- Rewiring the injured CNS: Lessons from the optic nerveExperimental Neurology, 2008
- Expression of Osteopontin in the Rat Retina: Effects of Excitotoxic and Ischemic InjuriesInvestigative Ophthalmology & Visual Science, 2008
- Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucomaThe Journal of cell biology, 2007
- Semiquantitative Optic Nerve Grading Scheme for Determining Axonal Loss in Experimental Optic NeuropathyInvestigative Ophthalmology & Visual Science, 2006
- Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J miceThe Journal of cell biology, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injuryNeuron, 1991