A primate model of nonarteritic anterior ischemic optic neuropathy

Celia S. Chen, Mary A. Johnson, Robert A. Flower, Bernard J. Slater, Neil R. Miller, Steven L. Bernstein

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE. Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic nerve (ON) stroke and a leading cause of sudden ON-related vision loss. A primate (p)NAION model is crucial to further understanding of the clinical disorder and can provide information regarding the pathophysiology of other central nervous system (CNS) ischemic axonopathies. In the current study, a primate model of NAION was developed, and short-and long-term responses to this condition were characterized. METHODS. pNAION was induced with a novel photoembolic mechanism. Short-and long-term responses were evaluated by minimally invasive testing (electrophysiology, fundus photography, indocyanine green and fluorescein angiography, and magnetic resonance imaging) and compared with histologic and immunohistochemical findings. RESULTS. Optic disc edema, similar to that observed in cases of human NAION was seen 1 day after induction, with subsequent resolution associated with the development of optic disc pallor. Magnetic resonance imaging (MRI) performed 3 months after induction revealed changes consistent with ON atrophy. Electrophysiological studies and vascular imaging suggest an ON-limited infarct with subsequent axonal degeneration and selective neuronal loss similar to that seen in human NAION. ON inflammation was evident 2 months after induction at the site of the lesion and at distant sites, suggesting that inflammation-associated axonal remodeling continues for an extended period after ON infarct. CONCLUSIONS. pNAION resembles human NAION in many respects, with optic disc edema followed by loss of cells in the retinal ganglion cell (RGC) layer and ON remodeling. This model should be useful for evaluating neuroprotective and other treatment strategies for human NAION as well as for other ischemic processes that primarily affect CNS white-matter tracts.

Original languageEnglish (US)
Pages (from-to)2985-2992
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number7
DOIs
StatePublished - Jul 2008

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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