Electrical Stimulation of Mammalian Retinal Ganglion Cells Using Dense Arrays of Small-Diameter Electrodes - Artificial Sight: Basic Research, Biomedical Engineering, and Clinical Advances - page 342

Furthermore, human chronic retinal implants must be capable of delivering
effective stimulation pulses over a period of many hours each day. To demon-
strate that electrical stimulation remained functional after longer periods of
time, two ganglion cells were stimulated continuously at 1-2 Hz for the longest
duration that was experimentally feasible in our setup: spikes could still be
evoked reliably after 4.5 hours, albeit with small threshold increases.
Miscellaneous Results
To ascertain that the applied electrical pulses directly stimulated ganglion cells, the
calcium channel blocker cadmium chloride 100-250M was applied to the bath
solution to abolish synaptic transmission. In all 10 cells tested, evoked spikes were
still observed after drug application, indicating that the observed spikes were not
produced by mechanisms involving calcium-dependent synaptic transmission.
To establish upper limits for electrical stimulation using our multi-electrode
arrays, several cells were stimulated with very high charge densities. Stimulation
at currents and charge densities several-fold above threshold tended to disrupt
the spontaneous and evoked spikes of ganglion cells, usually in a reversible
manner: spike height decreased until spikes could no longer be detected. In many
cells, spiking activity resumed after a period of several minutes. Local toxicity
or heating effects were likely responsible for disrupting ganglion cell spiking,
indicating that there is an upper ceiling for the optimal range of currents used in
stimulation using small array electrodes.
Discussion
Electrical stimulation of rat, guinea pig, and primate retina with dense, small-
diameter electrode arrays was achieved using low charge densities. Our multi-
electrode arrays closely resemble those currently in use for human patient testing
but contain much smaller electrodes at a much smaller electrode spacing. The
purpose of this study was to elucidate the basic stimulation parameters so that
the next generation of implants may incorporate a design using much smaller
electrodes than are currently in use.
An important concern regarding implantable stimulation devices is their
capability to deliver electrical current that is safe, yet efficient. As shown in
this study, a single ganglion cell (at most a few cells) can be induced to fire a
single spike (at most a few spikes) by using currents typically below 1A and
with charge densities below 010mC/cm 2 . The literature is inconclusive about
the safety of small electrodes for prosthetic implants: reported threshold values
range from 016mC/cm 2 [13] to 059mC/cm 2 [14] for small-diameter micro-
probes, whereas 035mC/cm 2 is the safe limit for stimulation with platinum
electrodes [28]. We conclude that small-diameter electrode arrays 8-12m
do not require dangerously high charge densities to achieve reliable spiking in
mammalian retina.