Wireless visual electrophysiology in conscious rats for preclinical drug testing

© 2014 Dr. Jason CharngAim: To develop a montage to measure electroretinogram (ERG) and visual evoked response without anaesthesia and apply to detect central penetrance for drug testing. Material and methods: Anaesthetised works were firstly undertaken to determine optimal electrode placements (3-month-old male Long-Evans rats, n = 6). Telemetry transmitters were implanted in rats (3-month-old male Long-Evans rats, n = 8), from which ERG and VEP in conscious rats are recorded. Using the telemetry montage, we investigated the effect commonly used laboratory anaesthetics (intramuscular ketamine:xylazine or inhalant isoflurane) has on visual electrophysiology. To test for central penetrance, rats (3-month-old male Long-Evans rats, n=8 each group) were implanted with telemetry transmitter and administered with either isoguvacine or muscimol. Both drugs are GABAa agonists, with the difference being muscimol readily crosses the blood-neural-barriers whereas isoguvacine does not. Therefore systemic administration of isoguvacine should return different ERG and VEP changes to local administration but the signal changes should be similar between local and systemic muscimol injections. The results of this experiment are compared to that of anaesthetised (3-month-old male Long-Evans rats, n=5 each group), conventional recordings to investigate anaesthesia confounds. Results: We show, for first time, wireless ERGs and VEPs are recordable in conscious rodents. Furthermore, the data indicates that the signals are stable for at least four weeks but commonly used laboratory anaesthesia alters waveform profiles. The GABAa agonists experiment suggests that the telemetry system is capable of detecting drug penetrance, however, the presence of anaesthesia confounds findings. Conclusion: We show that current conventional recording are confounded by anaesthesia and this novel system can potentially be used to detect drug penetrance. Moreover this system demonstrates potential for longitudinal studies, paving the way for neurodegenerative studies such as glaucoma in the future