Distal axonopathy with structural persistence in glaucomatous neurodegeneration

An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma....

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-03, Vol.107 (11), p.5196-5201
Main Authors: Crish, Samuel D, Sappington, Rebecca M, Inman, Denise M, Horner, Philip J, Calkins, David J
Format: Article
Language:English
Subjects:
Aging - pathology
Animals
Axons
Axons - metabolism
Axons - pathology
Biological Sciences
Biological Transport
Cells
Ganglia
Glaucoma
Glaucoma - complications
Glaucoma - pathology
Mice
Nerve Degeneration - complications
Nerve Degeneration - pathology
Neurons
Optic disk
Optic nerve
Retina
Retina - pathology
Rodents
Synapses
Visual pathways
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0913141107