Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that macaque retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision – however, this possibility has never been tested in the human retina. Here, the electrical activation properties of identified RGC types in the human retina were examined using large-scale, multi-electrode recording and stimulation ex vivo and were compared directly to results from macaque. Precise activation was often possible without activating overlying axon bundles, at low stimulation current levels similar to those observed in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce a nearly optimal evoked visual signal. These results reveal the possibility of high-fidelity vision restoration using bi-directional retinal implants.

Electrical stimulation of retinal ganglion cells (RGCs), which transmit visual information to the brain, is used in retinal implants to treat blindness caused by photoreceptor degeneration. However, the performance of existing clinical implants is limited by indiscriminate stimulation of many cells and cell types. Recent work in isolated macaque retina has shown the ability to precisely evoke spikes in the major RGC types by direct electrical stimulation at safe current levels, with single-cell, single-spike resolution and avoidance of axon bundle activation in many cases. However, these findings have not been verified in the human retina. Here, electrical activation of the major human RGC types was examined using large-scale, multi-electrode recording and stimulation and compared to results from several macaque retinas obtained using the same methods. Electrical stimulation of the major human RGC types closely paralleled results in macaque, with similar somatic and axonal stimulation thresholds, cellular and cell type selectivity of stimulation, avoidance of axon bundle stimulation by calibration, targeting of different cell types based on their distinct electrical signatures, and potential efficacy of real-time stimulus optimization for artificial vision. The results indicate that the macaque retina provides a quantitatively accurate picture of how focal electrical stimulation can be used in future high-resolution implants.

We report a new class of textiles with electrochemical functions which, when moistened by a conductive liquid (saline solution, sweat, wound fluid, etc.), generate DC voltage and current levels capable of powering wearable electronics on the go. Contrary to previously reported power generation techniques, the proposed fabrics are fully flexible, feel and behave like regular clothing, do not include any rigid components, and provide DC power via moistening by readily available liquids. Our approach entails printed battery cells that are composed of silver and zinc electrodes deposited onto a polyester fabric to generate power in the microwatt range. Electrochemical characterization of the discharge of a single printed battery cell in a 10 M NaOH electrolyte shows reproducible results with a sustained power level of ∼80 W for over 3 hours. Scalable DC power may also be achieved by connecting multiple battery cells in series via flexible and conductive E-threads. Indeed, a series connection of two battery cells is demonstrated to boost the generated voltage from 1.4 V to 2.5 V. Notably, this in-series printed battery arrangement is shown to successfully power a digital thermometer under both 10 M NaOH, a 0.5 M NaCl solution (mimicking human sweat), and Dulbecco's Phosphate-Buffered Saline solution (DPBS) (mimicking bodily fluid electrolytes). Overall, the proposed technology is expected to be of utmost significance for healthcare, sports, military, and consumer applications, among others.

Objective. Epiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells. Approach. In this work, a custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to stimulate and record RGCs in macaque retina ex vivo at single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation. Main results. On average, across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds (∼21%) while increasing axonal activation thresholds (∼14%), thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode. Significance. This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision.

Electrical stimulation of retinal ganglion cells (RGCs) with electronic implants provides rudimentary artificial vision to people blinded by retinal degeneration. However, current devices stimulate indiscriminately and therefore cannot reproduce the intricate neural code of the retina. Recent work has demonstrated more precise activation of RGCs using focal electrical stimulation with multi-electrode arrays in the peripheral macaque retina, but it is unclear how effective this can be in the central retina, which is required for high-resolution vision. This work probes the neural code and effectiveness of focal epiretinal stimulation in the central macaque retina, using large-scale electrical recording and stimulationex vivo. The functional organization, light response properties, and electrical properties of the major RGC types in the central retina were mostly similar to the peripheral retina, with some notable differences in density, kinetics, linearity, spiking statistics and correlations. The major RGC types could be distinguished by their intrinsic electrical properties. Electrical stimulation targeting parasol cells revealed similar activation thresholds and reduced axon bundle activation in the central retina, but lower stimulation selectivity. Quantitative evaluation of the potential for image reconstruction from electrically-evoked parasol cell signals revealed higher overall expected image quality in the central retina. An exploration of inadvertent midget cell activation suggested that it could contribute high spatial frequency noise to the visual signal carried by parasol cells. These results support the possibility of reproducing high-acuity visual signals in the central retina with an epiretinal implant.SIGNIFICANCE STATEMENT:Artificial restoration of vision with retinal implants is a major treatment for blindness. However, present-day implants do not provide high-resolution visual perception, in part because they do not reproduce the natural neural code of the retina. Here we demonstrate the level of visual signal reproduction that is possible with a future implant by examining how accurately responses to electrical stimulation of parasol retinal ganglion cells (RGCs) can convey visual signals. Although the precision of electrical stimulation in the central retina was diminished relative to the peripheral retina, the quality of expected visual signal reconstruction in parasol cells was greater. These findings suggest that visual signals could be restored with high fidelity in the central retina using a future retinal implant.