Anti-NOGO antibody neuroprotection in a rat model of NAION

Abstract

Purpose: To evaluate the efficacy and mechanisms of anti-NOGO receptor monoclonal antibody 11C7mAb in a rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods: The rNAION was induced in one eye of 20 Long-Evans rats, which were studied in 10 groups of two rats, each group containing a sham rat receiving intravitreal injections of vehicle and a treatment rat receiving intravitreal injections of 11C7mAb. Fellow eyes served as naïve controls. The rats were tested using flash electroretinograms (ERGs), flash visual evoked potentials (VEPs), and optical coherence tomography (OCT). Thirty days after induction, they were euthanized, and the eyes were prepared for immunohistochemistry (two groups), hematoxylin and eosin staining (two groups) or transmission electron microscopy (TEM; six groups). Results: Ninety-five percent of the VEP amplitude was preserved in eyes treated with 11C7mAb, versus 69% in the control eyes. Immunohistochemistry revealed a large reduction in microglia and extrinsic macrophages with axon sparing. In addition to axon preservation, TEM also showed reduced extracellular debris and only slight myelin damage compared with the vehicle-treated animals. There were no significant differences in retinal ganglion cell counts, nor was there a difference in optic nerve swelling as measured by OCT. ERGs were used to exclude eyes with retinal vascular occlusions, an occasional complication of the induction technique. Conclusions: The 11C7mAb preserves optic nerve integrity and reduces inflammation in rNAION. Translational Relevance: This study evaluates the efficacy of an anti-NOGO receptor antibody in a rat model of NAION, a disorder that currently has no universally-acknowledged treatment.