The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina

Abstract

Background/Aims: Retinal prostheses use electrical stimulation to restore functional vision to patients blinded by retinitis pigmentosa. A key detail is the spatial pattern of ganglion cells activated by stimulation. Therefore, we characterized the spatial extent of network-mediated electrical activation of retinal ganglion cells (RGCs) in the epiretinal monopolar electrode configuration. Methods: Healthy mouse RGC activities were recorded with a micro-electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic voltage pulses and cycling full-field light flashes. Results: Voltage tuning curves exhibited significant hysteresis, reflecting adaptation to electrical stimulation on the time scale of seconds. Responses decreased from 0 to 300 µm, and were also dependent on the strength of stimulation. Applying the Rayleigh criterion to the half-width at half-maximum of the electrical point spread function suggests a visual acuity limit of no better than 20/946. Threshold voltage showed only a modest increase across these distances. Conclusion: The existence of significant hysteresis requires that future investigations of electrical retinal stimulation control for such long-memory adaptation. The spread of electrical activation beyond 200 µm suggests that neighbouring electrodes in epiretinal implants based on indirect stimulation of RGCs may be indiscriminable at interelectrode spacings as large as 400 µm.

Spike-triggered average electrical stimuli as input filters for bionic vision—a perspective

“…First, because long recovery periods are not interleaved between successive pulses, the resolution with which voltage amplitudes can be probed is much higher for a fixed recording time, providing for a much more detailed voltage-response curve than in traditional studies (Jalligampala et al 2017). Second, by measuring the voltage-response function in the context of ongoing electrical stimulation, the adaptive phenomenon of desensitization (Weiland et al 2016) is held constant and the adaptation state of the retina is better matched to that of real-world prosthetic stimulation (Hosseinzadeh et al 2018). It will be informative to compare such white-noise generated stimulus-response curves to those generated under traditional methods in the same experiment.…”

Classification of pseudocalcium visual responses from mouse retinal ganglion cells

“…We used a 60-channel MEA to record extracellular voltage signals from RGCs. As detailed in previous studies (Hosseinzadeh et al, 2017; Jalligampala et al, 2017) we anesthetized the mice with isoflurane and then killed them by cervical dislocation before isolating retinal tissue from the pigment epithelium, sclera, and other tissues of the eye. Retinas were kept in a carbogenated (95% O 2 , 5% CO 2 ) artificial cerebrospinal fluid.…”

Hemispherical Microelectrode Array for Ex Vivo Retinal Neural Recording

“…To study retinal signaling and to improve the spatial and temporal resolution of electrical stimulation on the retina, various ex vivo and in vitro experiments have been performed using microelectrode arrays (MEAs) capable of stimulating and recording from individual retinal neurons [6,9,10].…”