Establishment of a novel alloxan-induced rabbit model exhibiting unique diabetic retinal neuropathy features assessed via ERG + VEP

Abstract

Background: Diabetic retinal neuropathy (DRN) leads to significant visual impairment; however, no existing animal model fully replicates its neural alterations, and inconsistent induction protocols with high mortality rates hinder long-term investigations.

Methods: Adult male rabbits were randomly assigned to four experimental groups, each receiving a single intravenous injection of varying doses of alloxan and one control group. The safety and efficacy of alloxan in inducing diabetes were evaluated to determine the optimal dose. At 9 weeks following injection with alloxan, retinal function was assessed using full-field electroretinography (ERG) and visual evoked potentials (VEPs). Retinal structure was examined in rabbits using spectral-domain optical coherence tomography (SD-OCT), Optos ultra-widefield (Optos UWF) false-color imaging, and widefield fundus fluorescein angiography (WF-FFA).

Results: Rabbits in the 80 mg/kg alloxan group exhibited fewer complications, lower mortality, and a higher model success rate compared to other groups. At 9 weeks post-injection, these rabbits demonstrated significantly elevated hemoglobin A1c and total cholesterol (p < 0.05) relative to controls. ERG revealed statistically significant reductions in oscillatory potential and b-wave amplitudes (p < 0.05), while VEP indicated decreased P2 amplitude (p < 0.001) and prolonged P2 latency (p < 0.05). SD-OCT, Optos UWF imaging, and WF-FFA demonstrated no significant changes in vascular abnormalities. Additionally, Hematoxylin and Eosin staining revealed retinal swelling (p < 0.05), and immunofluorescence confirmed glial activation and neuronal loss.

Conclusions: A single intravenous injection of 80 mg/kg alloxan effectively and safely induced DRN in rabbits, resulting in neural retina damage, thereby establishing this model as an ideal model for DRN research.

Keywords: ERG+ops; VEP; alloxan; diabetic retinal neuropathy; rabbit.