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Kelly Tenneson, Mark Vezina; Evaluation of Anesthetic Effects on Electroretinogram (ERG) Recording in Rats. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5346.
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Electroretinograms are a commonly used endpoint in non-clinical studies to evaluate the potential effects of new chemical entities on retinal function. The challenge when using animal models is that assessments must be done while the animals are anesthetized. Selection of the anesthetic agent and dose is therefore critical to obtain suitable results. Factors that must be taken into consideration are the length of the testing protocol relative to duration of the anesthesia and the anesthetic agent, possible interference of ERG response, and inter-animal sensitivity to anesthesia. We characterized the effect of various anesthetic agents on ERG responses and to evaluate duration of anesthesia of the effect in rats.
Rats (groups of 3 to 8 males; 100 to 300 g and approximately 6 to 12 weeks of age) were administered one of the following six 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), fentanyl, medetomidine and midazolam (FMM) or fentanyl, dexmedetomidine and midazolam (FDM). Animals were subsequently subjected to a standard ERG testing protocol; consisting of three scotopic, single flash stimuli and two photopic flicker stimuli. A reversal cocktail was administered to groups given FMM and FDM.
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 (2.5 cd●s/m2) b-wave amplitudes (647±280 and 626±148 uV, respectively) were approximately 2-fold higher than with other cocktails. Latency times were unaffected. FMM and FDM offered the most flexibility in anesthetic duration. Anesthesia lasted up to 2 hours in most animals, but administration of the reversal agent was effective within minutes of administration, which improves recovery and reduces risks associated with ocular drying and prolonged periods of anesthesia.
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, FMM and FDM were considered to be optimal for ERG recording, based on ERG waveforms obtained, levels and duration of anesthesia, and reversibility.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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