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
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Glyn Chidlow Andreas Ebneter John P. M. Wood Robert J. Casson
- چاپ و سال / کشور: 2011
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 NMDAinduced 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.
Acta Neuropathol (2011) 121:737–751 DOI 10.1007/s00401-011-0807-1 Received: 17 November 2010 / Revised: 27 January 2011 / Accepted: 29 January 2011 / Published online: 11 February 2011
