Electrical Stimulation of Mammalian Retinal Ganglion Cells With Multielectrode Arrays

Abstract

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micrometers. To increase the spatial resolution of artificial sight, electrodes much smaller than those currently in use are desirable. In this study, we stimulated and recorded ganglion cells in isolated pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal arrays of 61 platinum disk electrodes with diameters between 6 and 25 microm, spaced 60 microm apart. Charge-balanced current pulses evoked one or two spikes at latencies as short as 0.2 ms, and typically only one or a few recorded ganglion cells were stimulated. Application of several synaptic blockers did not abolish the evoked responses, implying direct activation of ganglion cells. Threshold charge densities were typically <0.1 mC/cm2 for a pulse duration of 100 micros, corresponding to charge thresholds of <100 pC. Stimulation remained effective after several hours and at high frequencies. To show that closely spaced electrodes can elicit independent ganglion cell responses, we used the multielectrode array to stimulate several nearby ganglion cells simultaneously. From these data, we conclude that electrical stimulation of mammalian retina with small-diameter electrode arrays is achievable and can provide high temporal and spatial precision at low charge densities. We review previous epiretinal stimulation studies and discuss our results in the context of 32 other publications, comparing threshold parameters and safety limits.

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

“…5) that are about two orders of magnitude below the damage threshold current density (Butterwick et al 2007;Cohen et al 2011). These current thresholds are smaller than most reported values (reviewed in Sekirnjak et al 2006). We attribute the low threshold to the tight tissue-electrode contact and to monophasic pulses that efficiently polarize cell membranes (Plonsey and Barr 2007).…”

“…In the epiretinal configuration the stimulation electrode is close to the retinal projection neurons, the ganglion cells, whereas in the subretinal configuration the stimulation electrode is close to the outer retina. The activation of preselected retinal circuitry is currently investigated in both configurations: Examples include the selective activation of retinal ganglion cells with small electrodes (Sekirnjak et al 2006(Sekirnjak et al , 2008 and the preferential activation of bipolar cells or photoreceptors with sinusoidal stimuli with appropriate frequencies (Freeman et al 2010). Restricted stimulation geometry, however, hampers a thorough investigation of the biophysical mechanisms underlying neuronal stimulation in the retina (but see Fried et al 2009).…”

Sinusoidal Electrical Pulse More Efficiently Evokes Retinal Excitation than Rectangular Electrical Pulse in Retinal Prostheses

“…Sekirnjak et al reported that reducing the electrode area can limit the range of stimulated retinal ganglion cells to a spatially confined region. (14) The localization of stimulation indicates that the excitation of the retina and the primary visual cortex are both localized. Thus, the localization of phosphenes is suggested to be achieved by optimizing the stimulation waveform.…”

“…(12) The optimum pulse duration and frequency for retinal ganglion cell activation (with respect to stimulation effectiveness) has been studied in vitro. (13)(14)(15) However, the optimal stimulation waveform shape remains unknown. Accordingly, a rectangular pulse may not be optimal as the stimulation waveform.…”

Elektrot Etkileşimi ve Uyartım Eşiğinin Azaltılmasına Yönelik Sonlu Elemanlar Yöntemi Tabanlı Yeni Bir Retina Uyartım Stratejisi

“…Görsel protez sistemleri, görsel yolda zarar görmüş bölgelerin bypass edilerek fonksiyonel olarak uygun bozulmadan kalan bölgelerdeki sinir hücrelerini o bölgeye yerleştirilen bir elektrot dizisi ile elektriksel olarak uyartarak görsel restorasyonun yeniden kazanımını sağlamayı hedefleyen sistemlerdir. Son yıllarda, elektronik, minyatürizasyon, malzeme, mikroelektronik paketleme gibi farklı alanlardaki ilerlemeler retina protezlerinin geliştirilmesini mümkün kılmıştır [5,6]. Retina protezleri elektriksel uyartımın gerçekleştirileceği mikroelektrot dizisinin implante edileceği hedef retina bölgesine bağlı olarak 3 ana kategoride sınıflandırılabilir.…”