Establishment and assessment of a rat model of nonarteritic anterior ischemic optic neuropathy

Abstract

Objective To establish and evaluate a rat model of nonarteritic anterior ischemic optic neuropathy (NAION). Methods The rats were randomly divided into control group (n=13), sham laser group (n=11) and NAION group (n=23). The right eye was set as the experimental eye. NAION model was induced by directly illuminating the optic nerve (ON) of the right eye with 532 nm green laser, after intravenous infusion with the photosensitizing agent Rose Bengal. Sham laser treatment consisted of illuminating the ON region with 532 nm laser without Rose Bengal injection. Rats in control group underwent no intervention. The appearance of optic disc was observed with funduscope at 12 hours, 1, 3, 7, 28 days post-illumination. The histologic changes in the retina and ON of the NAION model were evaluated qualitatively with hematoxylin and eosin (HE) staining and transmission electron microscopy. The retrograde-labeled retinal ganglion cells (RGC) were counted on photographs taken from retinal flat mounts in a masked fashion. Results The optic disc in NAION eyes were swollen 3 days after photodynamic treatment. HE-stained longitudinal ON sections of NAION revealed vacuolar degeneration on day 3 after induction. Besides, ultrastructural study showed axonal edema and collapsed sheaths in the ischemic optic nerve at the same time point after modeling. ON edema resolved 7 days after induction. The final results revealed optic disc atrophy, extensive axonal loss, severe glial scar, and RGC death in large numbers 4 weeks after modeling. There were no aforementioned manifestations in control and sham laser group. The RGC density of the right eyes was statistically significantly lower in NAION group than that in control group and in sham laser group (t=−14.142, −14.088; P=0.000, 0.000). The survival rate of RGC was statistically significantly lower in NAION group than in control group and in sham laser group (t=−17.048, −16.667; P=0.000, 0.000). There was no difference of RGC density and survival rate of RGC between control and sham laser group (t=0.050, 0.348; P=0.961, 0.731). Conclusion A rat model of NAION was established successfully by photodynamic treatments with Rose Bengal, which induce optic nerve damage and RGC death. Key words: Optic neuropathy, ischemic; Retinal ganglion cells; Disease models, animal