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Glyn Chidlow, Matthew C. Holman, John P. M. Wood, Robert J. Casson; Spatiotemporal Characterization of Optic Nerve Degeneration after Chronic Hypoperfusion in the Rat. Invest. Ophthalmol. Vis. Sci. 2010;51(3):1483-1497. doi: 10.1167/iovs.09-4603.
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© ARVO (1962-2015); The Authors (2016-present)
Permanent, bilateral occlusion of the common carotid arteries (2VO) is an established model of chronic hypoperfusion. Previous studies have noted the vulnerability of the optic nerve (ON) to 2VO; however, little information is available regarding the spatiotemporal pattern of axonal degeneration and the accompanying glial cell responses. The present study was conducted to investigate these topics.
At various times after surgery, ONs were removed for mRNA or Western blot analysis or to be processed for histology and immunohistochemistry.
2VO precipitated an infarct within the proximal ON, whereas the retinal ganglion cells, unmyelinated axons of the optic nerve head, and the distal portion of the ON were initially preserved. The onset of degeneration was rapid, with disturbances in fast axonal transport occurring by 6 hours, damage to the axonal cytoskeleton in the proximal ON detectable by 24 hours, and complete axonal loss within the infarcted area manifest within 3 days. Wallerian degeneration of the distal segment of the ON proceeded thereafter, with almost complete loss of the ON axonal cytoskeleton evident by 30 days. Degradation of the axonal cytoskeleton was accompanied by increasing microglial activation and proliferation and a delayed infiltration of macrophages into the lesion site. Robust and persistent upregulation of stress proteins by astrocytes and oligodendrocytes, which correlated with axonal damage, was found throughout the ON after 2VO. Extracellular matrix remodeling was evident in the optic nerve head and proximal ON.
2VO causes rapid degeneration of the ON, with some similarity to rodent ischemic optic neuropathy.
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