Abstract
Purpose: :
The ERG is known to be a sensitive marker of early retinal functional deficits in animal models of diabetic retinopathy and in humans with diabetes. In addition, strain differences in the development of retinal lesions have been documented for several animal models of induced ocular disease. As such, a review of the historical data from Sprague Dawley (SD) and Long Evans (LE) rats used for the STZ-induced diabetic retinopathy in our laboratory was conducted to evaluate potential strain differences.
Methods: :
Scotopic (3 light intensities) and photopic (1 Hz) flicker ERGs were recorded under ketamine/xylazine anesthesia prior to STZ administration then weekly for 4 weeks. ERGs were also recorded from a concurrent untreated control. STZ was administered intravenously (60 mg/kg) and blood glucose measured at least twice weekly. Animals with glucose levels > 250 g/dL were considered diabetic. Parameters evaluated included b-wave amplitude, implicit time and oscillatory potential (OP) amplitude. Eyes were also evaluated at 4 weeks for morphological changes by histopathology and/or OCT and/or fluorescein angiography (FA).
Results: :
All animal blood glucose levels were between 300-500 g/dL and considered diabetic. There were no morphological changes detected by histopathology, OCT or FA after 4 weeks. Scotopic b-wave amplitude was slightly elevated at Week 1 and decreased only by Week 4 in LE rats. In contrast, SD rats exhibited an immediate decrease in scotopic b-wave amplitude commencing Week 1. LE rats had a dramatic reduction of photopic 1Hz flicker amplitude during Week 1 that remained low but stable through Week 4. SD rats however did not display any significant effect at the photopic 1 Hz. OPs 1-4 were analyzed with the most consistent amplitude reductions in both strains occurring with the clinically relevant OP2 up to Week 2. After Week 2, OP amplitudes became more variable with OP2 remaining the most consistently reduced.
Conclusions: :
Strain differences noted in this review of historical early ERG data in the STZ diabetic retinopathy model in our laboratory are consistent with those reported in other ocular models. This is an important consideration when comparing data from the literature or when selecting the animal model for experimental purposes.
Keywords: diabetic retinopathy • electroretinography: non-clinical • retina