Intra-Retinal Electrical Stimulation: Comparison to Epi- and Sub-Retinal Approaches

Abstract

Purpose: To assess potential improvements in retinal stimulation using close positioning of the electrodes, thresholds were measured with electrodes placed epiretinally, subretinally and penetrating inside the inner and outer plexiform layers (IPL and OPL). The strength-duration relationship of direct and network-mediated responses was determined for each location.

Methods: The whole-cell recordings of action potentials were obtained from RGCs of Long Evans rat retina in vitro. Cathodic and anodic pulses of 0.1-20ms in duration were applied via electrodes in four positions: epiretinal, IPL, OPL, and subretinal. Epiretinal and intraretinal stimulation was applied via 5μm glass pipette electrodes, while subretinal electrode was a 40μm disc.

Results: Stimulation thresholds strongly varied with pulse polarities and electrode locations, but the shape of the strength-duration relationship was independent of electrode location and stimulus polarity. Direct stimulation threshold exhibited chronaxy of about 1ms, while the network threshold continued a constant-slope decrease with increasing pulse duration, at least up to 20ms. The lowest stimulation threshold for direct response was cathodic epiretinal: 1.5μA at 2ms, with corresponding network threshold of 5μA. Epiretinal placement had the highest selectivity for direct stimulation without evoking network response: thresholds ratio was 3.3 for 2ms pulses. Insertion of the electrode into IPL increased both cathodic thresholds: to 3 and 5.5μA, respectively, but decreased anodic thresholds: from 7.9 and 15μA to 4.3 and 8.7μA. In subretinal placement the network thresholds were lower than direct ones, and anodic pulses had lower thresholds (1.5 and 2.2μA for the network and direct responses at 4ms) than cathodic (17.9 and 23.4μA). Upon insertion of the electrode into OPL the thresholds for both polarities decreased, and the direct thresholds remained about twice higher than the network with 4 ms pulses.

Conclusions: Intraretinal positioning of the electrodes may provide better and more stable proximity to the target cells than the epiretinal or sub-retinal arrays. However, electrodes on epiretinal surface still have the lowest thresholds and highest selectivity of direct stimulation of RGCs. OPL position has lower thresholds than subretinal, and the highest selectivity of the network stimulation (7.7) is achieved at longest pulse durations (20ms) for both polarities.

Keywords: 688 retina • 508 electrophysiology: non-clinical