Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy

Abstract

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 histologic, 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 1 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 2 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 histologic 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.