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Abstract #9874 Published in IGR 5-3
Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy
Bernstein SL; Guo Y; Kelman SE; Flower RW; Johnson MAInvestigative Ophthalmology and Visual Science 2003; 44: 4153-4162
PURPOSE: Anterior ischemic optic neuropathy (AION) is caused by sudden loss of vascular supply to retinal ganglion cell (RGC) axons in the anterior portion of the optic nerve and is a major cause of optic nerve dysfunction. There has been no easily obtainable animal model of this disorder. The current study was conducted to design a novel model of rodent AION (rAION), to enable more detailed study of this disease. METHODS: A novel rodent photoembolic stroke model was developed that is directly analogous to human AION. Using histological, electrophysiological, molecular- and cell biological methods, the early changes associated with isolated RGC axonal ischemia were characterized. RESULTS: Functional (electrophysiological) changes occurred in RGCs within one day after rAION, with a loss of visual evoked potential (VEP) amplitude that persisted in the long term. The retinal gene expression pattern rapidly changed after rAION induction, with an early (< 1 day) initial induction of c-Fos mRNA, and loss of RGC-specific gene expression. RGC-specific protein expression declined two days after detectable mRNA level changes, and immunostaining suggested that multiple retinal layers react to isolated RGC axonal ischemia. CONCLUSIONS: rAION rapidly results in electrophysiological and histological changes similar to clinical AION, with reactive responses in primary and supporting neuronal cell layers. The rAION model can enable a detailed analysis of the individual retinal and optic nerve changes that occur after optic nerve stroke, which may be useful in determining possible therapeutic interventions for this disorder.
Dr. S.L. Bernstein, Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. slbernst@umaryland.edu
Classification:
10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy
