Abstract
Purpose :
Electroretinograms are a commonly used endpoint in non-clinical studies to evaluate the potential effects of new chemical entities on retinal function. In animal models, this assessment must be done under anesthesia; therefore, selection of the anesthetic agent and dose is critical to obtain suitable results. Some of the factors that must be taken into consideration are: the length of the testing protocol relative to duration of the anesthesia, the anesthetic agent, as some can interfere with or modify ERG response, and inter-animal sensitivity to anesthesia. We characterized the effect of multiple anesthetic agents on ERG response and evaluated the recovery time in rats.
Methods :
Sprague-Dawley Crl:CD(SD) and Wistar Han (up to 5 males/group; 100 to 300 g and approximately 6 to 12 weeks of age) rats were administered one of the following combinations: ketamine / acepromazine (KA), ketamine / xylazine / acepromazine (KXA) or ketamine / xylazine (KX; administered at two dose levels 50/5 mg/kg and 75/7.5 mg/kg) and were subsequently subjected to a standard ERG testing protocol; consisting of three scotopic, single flash stimuli and two photopic flicker stimuli.
Results :
The anesthetic used was shown to have a major impact on the amplitude of the ERG responses. KXA and KX (75/7.5 mg/kg) scotopic 0 dB b-wave amplitudes (647±280 and 626±148 uV, respectively) were approximately 2-fold higher than the response when KA or KX (50/5 mgkg) (320±57 and 329±48 uV, respectively). Latency times were unaffected. Recovery time was the shortest with KXA (104±19 min), while animals took at least 20 minutes longer to recover with other cocktails.
Conclusions :
In conclusion, the anesthetic agent for ERG recording has a significant impact on the magnitude of the response, which needs to be taken into consideration during the study design phase and when comparing between results in different studies. In this study, KX-75/7.5 provided an appropriate level and duration of anesthesia and good quality waveform.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.