Abstract
Purpose: :
Electroretinography (ERG) plays a pivotal role in nonclinical toxicity testing of ocular drugs. Reproducability at each time point is crucial. Assessments typically use human ERG equipment. Laboratory animals must be sedated for ERG assessment. Technical modifications and sedation techniques that were developed to optimize ERG assessment in non-human primates, dogs, rabbits, and rats are presented.
Methods: :
Data was collected according to ISCEV recommendations with a UTAS E-3000 Visual Electrodiagnostic System (LKC Technologies, Inc). Non-human primates and dogs were laid prone with the head on the Ganzfeld chinrest. Warming was limited to recovery. Standard ERG-Jet Electrodes were used. A raised platform was used for rabbits and rats to provide elevation and placement of the head into the Ganzfeld dome. A modified electrode was constructed for the rat measurements. Warming was occasionally necessary for rabbits and necessary for the rat. Non-human primates were sedated with ketamine and dexmedetomidine. Sedation of dogs required ketamine and acepromazine. Rabbits and rats were successfully sedated with ketamine and xylazine.
Results: :
Sedation procedures for non-human primates were easily reproduced across animals and over multiple time points. For dogs and rabbits, modifications were required to provide enough sedation to avoid excitability, but not enough interfere with electrode placement. For rabbits and rodents, an elevated platform was developed that allowed for ease of placement in the Ganzfeld dome. This platform was used with or without additional warming to maintain body temperature during the collection procedure. In all cases, procedures were developed that could be easily reproduced across time points.
Conclusions: :
Measurement of ERGs in non-human primates required minimal modification of equipment designed for human ERG measurement. Standard electrodes can be used, minimal body temperature maintenance is required and standard sedation procedures are sufficient. Minimal equipment modification is needed for dogs; however, a fine balance is required to achieve optimal sedation. For rabbits, technical modifications primarily involve the use of a raised platform to elevate and orient the head within the Ganzfeld dome. Common sedation practices for rabbits are sufficient for use during ERG measurements. Rats required the use of a raised platform, a warming pad and specially-constructed electrodes. These techniques and procedures allow for reduced variability between repeated ERG measurements conducted as part of non-clinical ocular safety and toxicity testing.
Keywords: electroretinography: non-clinical • comparative anatomy • retina