Optic Nerve Disease and Axon Pathophysiology

Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
International Review of Neurobiology (Impact Factor: 1.92). 12/2012; 105:1-17. DOI: 10.1016/B978-0-12-398309-1.00002-0
Source: PubMed


Optic neuropathy is the most common cause of irreversible blindness worldwide. Although the most common optic neuropathy is glaucoma, there are also many other optic neuropathies, for example, those associated with multiple sclerosis, giant cell arteritis, ischemia, and many other diseases. In almost all cases, the pathogenesis involves injury to the retinal ganglion cell axon, with consequent somal and axonal degeneration. This chapter reviews the clinical and pathophysiological properties associated with three of the most common optic neuropathies, as well as recent findings in understanding axonal degeneration. It concludes with a status report on therapies for optic nerve disease, including axoprotection, an approach being studied that has the goal of maintaining axonal integrity and function after injury.

Download full-text


Available from: Alireza Ghaffarieh, Dec 13, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Injuries to CNS axons result not only in Wallerian degeneration of the axon distal to the injury, but also in death or atrophy of the axotomized neurons, depending on injury location and neuron type. No method of permanently avoiding these changes has been found, despite extensive knowledge concerning mechanisms of secondary neuronal injury. The autonomous endoplasmic reticulum (ER) stress pathway in neurons has recently been implicated in retrograde neuronal degeneration. In addition to the emerging role of ER morphology in axon maintenance, we propose that ER stress is a common neuronal response to disturbances in axon integrity and a general mechanism for neurodegeneration. Thus manipulation of the ER stress pathway could have important therapeutic implications for neuroprotection. ANN NEUROL 2013. © 2013 American Neurological Association.
    Annals of Neurology 12/2013; 74(6). DOI:10.1002/ana.24005 · 9.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cell cycle re-entry is one of the key processes in neuronal apoptosis. Previous studies have shown that Ski-interacting protein (SKIP) played an important role in cell cycle re-entry. However, its expression and function in optic nerve injury are still with limited acquaintance. To investigate whether SKIP is involved in retinal ganglion cells (RGCs) death, we performed an optic nerve crush (ONC) model in adult rats. Western blot analysis revealed that up-regulation of SKIP was present in retina at 5 days after ONC. Immunofluorescent labeling indicated that up-regulated SKIP was found mainly in RGCs. We also investigated co-localization of SKIP with active-caspase-3 and TUNEL (apoptotic markers) -positive cells in the retina after ONC. In addition, the expression of SKIP was increased in parallel with P53 and P21 in retina after ONC. All these results suggested that up-regulation of SKIP in the retina was associated with RGCs death after ONC.
    Journal of Molecular Histology 07/2014; 45(6). DOI:10.1007/s10735-014-9589-9 · 1.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The rat optic nerve is a useful model for stem cell regeneration research. Direct injection into the rat optic nerve allows delivery into the central nervous system in a minimally-invasive surgery without bone removal. This technique describes an approach to visualization and direct injection of the optic nerve following minor fascial dissection from the orbital ridge, using a conjunctival traction suture to gently pull the eye down and out. Representative examples of an injected optic nerve show successful injection of dyed beads.
    Journal of Visualized Experiments 05/2015; 2015(99). DOI:10.3791/52249 · 1.33 Impact Factor
Show more