gms | German Medical Science

Objective: To eliminate or suppress pathological electrical activity in the retina that occurs upon photoreceptor degeneration and that compromises the efficiency of retinal ganglion cell (RGC) stimulation by an electrical prosthesis.

Methods: Electrophysiological recordings were obtained in vitro from retinae of wild type (WT) and rd10 mice – an animal model of retinal degeneration – using multi electrode arrays (MEA). Retinae were isolated from animals at the age of 3-4 months. Local field potentials (LFP) and spike activity of RGCs were recorded and RGCs were stimulated electrically. The effects of different agonists at GABAA receptors on oscillatory activity were investigated. Differences between stimulation with single biphasic electrical pulses and stimulation with pulse trains were studied.

Results: Previously, we had found two major differences between WT and rd10 retina. First, rd10 retina showed a pathological rhythmic activity in form of oscillations in the LFP at a frequency of around 3-6 Hz. Second, using single biphasic stimulation pulses, we found that the efficiency of electrical stimulation – measured as ratio of spike rate after and before the stimulation pulse – was lower in rd10 retina than in WT retina. We now extended these investigations to stimulus trains of different frequencies, e.g 1, 2 and 5 Hz pulses. In previous experiments we showed that the pathological rhythmic activity in rd10 retina can be abolished by the inhibitory neurotransmitter GABA as well as by diazepam, an allosteric modulator of the benzodiazepine family acting at GABAA receptors. Most importantly, blockade of oscillations increased the efficiency of electrical stimulation to values similar to those observed in WT retina. We now extended these findings to flunitrazepam and lorazepam, two other members of the benzodiazepine family.

Conclusion: In rd10 retina, pathological oscillatory activity seems to reduce the efficiency of electrical stimulation. We found that the three most commonly used benzodiazepines abolished oscillations and improved stimulation efficiency to values similar to WT retina. This study may open the way to a therapy that supports electrical stimulation by retinal prostheses with pharmacological treatment.

Acknowledgement: The study was supported by the DFG grants MU-3036/3-3, WA-1472/6-3, JO-1263/1-3 and Pro-Re/Projekt/Johnen-Diarra.1-2015.