Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

Abstract

Eickenscheidt M, Jenkner M, Thewes R, Fromherz P, Zeck G. Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array. J Neurophysiol 107: 2742-2755, 2012. First published February 22, 2012 doi:10.1152/jn.00909.2011.-Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array-insulated by an inert oxideallows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.

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

“…Our results confirm earlier studies which all find a decrease in electrical response with increasing distance from the stimulating electrode [8, 9, 20]. According to our previous report, the fraction of responsive RGCs in wild type mice on a ‘standard’ MEA (30 µm electrode diameter and 200 µm interelectrode distance) diminished speedily from about 50% at 200 µm to 20% at 283 µm with little additional drop up to 1000 µm [13].…”

“…As is common, using a monopolar electrode configuration in which the return electrode is implanted in a distant part of the eye or body, the flow of current through the retina near the electrode is approximately perpendicular to the surface of the retina [7]. Accordingly, for examinations of the spatial spread of electrical stimulation, the two configurations can be considered equivalent to a first approximation [8]. …”

“…In an earlier study Stett et al used a bar-like spatial stimulation pattern (0.8, 1.2 and 1.6 V amplitude) by selecting a row or a column on a 8× 8 MEA (diameter 10 µm, spacing 100 µm) which also yielded an increase in spike rate out to at least 100 µm in the chick retina [10]. Eickenscheidt et al showed that rectangular cathodal epiretinal stripe-like stimulation (areas 100 x1000 µm 2 , step spacing 50 µm) across a multicapacitor array can evoke responses in rabbit ON RGCs which extends over HWHM distance of 230 µm [8]. Lorach et al reported both the smaller (∼100 µm) and larger (∼250 µm) HWHM values in healthy and degenerated rat retina using a subretinal photovoltaic electrode array [11].…”

The retina-prosthesis interface in two rat models of retinitis pigmentosa and functional changes associated with photoreceptor loss.

“…Direct stimulation of the RGCs results in a 1:1 ratio of pulse to action potential while stimulating the BCs results in a burst of RGC activity (Eikenscheidt et al, 2012). This supports the theory that stimulating through BCs allows the signal to be processed by the retinal circuit, potentially leading to a better approximation of normal vision.…”

Functionality and Performance of the Subretinal Implant Chip Alpha AMS

“…(2) Ex vivo experiments have verified the stimulating effect on the retina of inward-directed currents. (3,4) The phosphene perceptions evoked by subretinal implants may be attributed to the depolarization of the PSTs by transretinal currents.…”