The purpose of this study is to compare power consumed at the electrode-retina interface between rectangular current controlled and voltage controlled stimulus pulses

Davuluri, Navya

Nimmagadda, Kiran

Weiland, James D.

Caltech Authors - Main

ARVO 2016 Annual Meeting Abstracts
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/ 
to access the versions of record.
Methods: Under anesthesia, the retina from rabbits was isolated 
and perfused in Ames Ringer. Large ganglion cells were selected for 
whole-cell recording using dim red or IR Nomarski illumination. 
A small hole was made in the inner limiting membrane to allow 
pipette access. The frequency vs. current firing properties of the 
ganglion cell were studied using 100pA current steps. Next, a thin 
insulated 100µm diameter Pt stimulus electrode was positioned at 
a 30 degree angle near the axon hillock/soma approximately 50µm 
above the retina. A series of 0.5msec ascending cathodic, followed 
by anodic current pulses (20msec apart) were used to examine how 
firing threshold varied laterally with soma proximity in 100µm steps. 
After recording, the morphology of the dye-filled ganglion cell was 
imaged and processed with anti-lucifer yellow antibodies for confocal 
microscopic reconstruction. The morphology of selected cells were 
entered into Neurolucida for segmentation, fitted with ion channels 
in NEURON, and imported into a novel electromagnetic-neuronal 
dynamics modeling program to simulate extracellular stimulation.
Results: When current steps were injected into the alpha cell 
body, a large pipette current was needed to elicit action potential 
threshold averaging 500±170pA (n=5 cells; mean ± std. dev). Some 
spike adaptation to firing was observed. Using epiretinal stimulus 
electrodes, action potentials were only generated by cathodic current 
pulses. When the electrode was placed adjacent to the cell body at the 
axon hillock region, thresholds for activation averaged 10.8±11.3nC 
(n= 5 cells; mean ± std. dev.). The spatial threshold for extracellular 
stimulation of the ganglion cells by the Pt electrode was localized to 
a region ~100µm around the initial segment/axon hillock of the cell 
body.
Conclusions: Large thinly insulated epiretinal stimulus electrodes 
activate action potentials in alpha ganglion cells in a spatially 
localized manner near the initial segment/soma region of the retinal 
ganglion cell. Synaptic activity may alter spike threshold.
Commercial Relationships: Ethan D. Cohen, None; 
Esra Neufeld; Hazael Montanaro, None; Maria I. Iacono, None; 
Leonardo M. Angelone, None; Wolfgang Kainz, None
Program Number: 3717 Poster Board Number: D0178
Presentation Time: 11:00 AM–12:45 PM
Electric stimulus duration alters network-mediated responses 
depending on retinal ganglion cell type
Maesoon Im1, 2, Shelley I. Fried2, 3. 1Ophthalmology, Henry Ford 
Hospital, Northville, MI; 2Boston VA Healthcare System, Boston, 
MA; 3Neurosurgery, Massachusetts General Hospital/HMS, Boston, 
MA.
Purpose: Despite some recent progress with retinal prosthetics the 
optimal duration for the electric stimulus remains unknown. Recently, 
we reported that an identical electric pulse elicits distinct responses 
in ON and OFF types of retinal ganglion cells (RGCs). The temporal 
properties to repetitive stimuli were also different in the two types. 
Thus, we hypothesize that varying the duration of the stimulus 
would alter the responses in different ways across different types of 
RGCs, thus raising a possibility to selectively activate one type over 
the other. Here, we systematically investigated network-mediated 
responses in various types of RGCs as a function of stimulus 
duration.
Methods: Cell-attached patch clamp was used to record spikes from 
RGCs in the rabbit retina explant. RGCs were classified as ON or 
OFF cells by their response to stationary flashes and further classified 
as Brisk Transient (BT) or Brisk Sustained (BS) subtypes by their 
electric responses. After cell type classification, monophasic half-
sinusoidal stimuli with durations of 5-100ms and amplitudes adjusted 
to keep total charge constant were presented to targeted RGCs. Each 
stimulus was repeated 7 times. We recorded the spiking activity in 7 
ON BT, 10 ON BS, 8 OFF BT, and 14 OFF BS cells.
Results: The pattern of network-mediated responses was unique for 
each type of RGC across a wide range of stimulus durations. We 
found that: 1) In ON cells, there was a distinct difference between 
BT and BS subtypes in number of spikes elicited by same stimulus 
duration but the distinction was less clear across OFF subtypes. 2) 
Across the durations tested, both types of ON cells showed dramatic 
changes in the number of evoked spikes while OFF cells showed 
smaller changes in their responses. 3) This disparity between ON and 
OFF cells resulted in the ratio of spikes elicited by the two types to be 
maximized at a stimulus duration of ~10 ms.
Conclusions: ON and OFF types of RGCs exhibited fundamental 
differences in responses to a wide range of durations of the electric 
stimulus, resulting in variable levels of ON vs. OFF selectivity at 
different durations. Together with our previous report that an electric 
stimulus evokes more physiological responses from ON cells than 
OFF cells, the finding here of a stimulus duration that maximizes the 
ON/OFF response ratio may offer enhanced clinical guidelines to 
retinal prosthetic community.
Commercial Relationships: Maesoon Im; Shelley I. Fried, None
Support: Boston VA Healthcare System (1I01RX000350-01A1) and 
NIH (R01EY023651)
Program Number: 3718 Poster Board Number: D0179
Presentation Time: 11:00 AM–12:45 PM
Relative power consumption at the electrode-retina interface 
during retinal stimulation with voltage versus current controlled 
stimulus pulses
Kiran Nimmagadda2, 3, Navya Davuluri4, James D. Weiland1, 4. 
1Ophthalmology, USC, Los Angeles, CA; 2Neuroscience Graduate 
Program, University of Southern California, Los Angeles, CA; 
3USC - Caltech MD/PhD Program, Los Angeles, CA; 4Biomedical 
Engineering, University of Southern California, Los Angeles, CA.
Purpose: The purpose of this study is to compare power consumed at 
the electrode-retina interface between rectangular current controlled 
and voltage controlled stimulus pulses.
Methods: Eleven Long Evans female rats under anesthesia were used 
for this in-vivo study. A 75 um diameter cylindrical Pt-Ir electrode 
was inserted into the left eye, and placed 50-100 um from the retina. 
Charge balanced biphasic voltage-controlled and current-controlled 
stimulus pulses of varying pulse width and amplitude were delivered 
to the retina. The pulse widths were 0.3 ms, 0.5 ms, 1 ms, and 2 
ms. For each pulse width, voltage and current-controlled pulse 
trains with charge levels from 10 nC to 60 nC were delivered to the 
retina. An oscilloscope was used to measure and record the voltage 
waveform of the stimulus pulses at the electrode-retina interface. A 
sense resistor in the stimulus current path was used to measure and 
record the current waveform delivered to the retina. As previously 
reported, electrically evoked responses (EERs) were recorded from 
the superior colliculus (SC) in response to the retinal stimulation.
Results: The voltage and current waveforms delivered to the retina 
were used to measure the power consumed at the electrode-retina 
interface during the cathodic phase for each stimulus condition. For 
stimulus pulse widths of 0.3 ms, 0.5 ms, and 1 ms, there was no 
statistically significant difference between the power consumed by 
the voltage-controlled pulses versus the current-controlled pulses 
(student t-test, p > 0.05) at all charge levels tested. For stimulus pulse 
width of 2 ms, there was no statistically significant difference in 
the power consumed for stimulus charge levels of 20 nC and 30 nC 
(student t-test, p > 0.05), while voltage pulses consumed significantly 
more power than current pulses for charge levels of 40 nC and 50 nC 
(student t-test, p < 0.05).
ARVO 2016 Annual Meeting Abstracts
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/ 
to access the versions of record.
Conclusions: In general, there is no significant difference in the 
power consumed at the electrode-retina interface between voltage 
and current controlled stimulus pulses, except for long pulse widths 
like 2ms and charge levels higher than 40 nC. This needs to be taken 
into consideration in combination with our previously reported results 
comparing the EERs in response to voltage versus current stimulus 
pulses when determining the most efficient stimulus parameters for 
electronic retinal prostheses.
Commercial Relationships: Kiran Nimmagadda; Navya Davuluri, 
None; James D. Weiland, None
Support: NSF CBET-1343193 and Research to Prevent Blindness
Program Number: 3719 Poster Board Number: D0180
Presentation Time: 11:00 AM–12:45 PM
Surgical feasibility of wide-field dual-array suprachoroidal–
transretinal stimulation (STS) prosthesis in middle-sized animals
Takeshi Morimoto2, Hiroyuki Kanda2, Tomomitsu Miyoshi3, 
Takao Endo1, Tibor K. Lohmann4, 2, Kohji Nishida1, 
Takashi Fujikado2. 1Ophthalmology, Osaka Univ Graduate Sch 
of Med, Suita, Japan; 2Applied Visual Science, Osaka University 
Graduate School of Medicine, Suita, Japan; 3Integrative Physiology, 
Osaka University Graduate School of Medicine, Suita, Japan; 
4Ophthatmology, Aachen RWTH Aachen University, Aachen, 
Germany.
Purpose: To investigate the feasibility of implanting a newly 
developed wide-field dual-array suprachoroidal–transretinal 
stimulation (STS) prosthesis in healthy dogs and cats.
Methods: Three healthy dogs and three healthy cats were used in this 
study. The STS dual array consisted of two arrays with 25 electrodes. 
The arrays were implanted into a scleral pocket of each of three 
healthy beagle dogs and three healthy cats under general anesthesia. 
Color fundus photography and Optical coherence tomography (OCT) 
were performed postoperatively. The animals were euthanatized after 
the experimental period and the retinas were evaluated histologically.
Results: All the prostheses were successfully implanted without 
complications, and no serious complications occurred during 
the experimental period. The fixation of the implant was stable 
throughout the experimental period. Fundus photographs and OCT 
revealed no serious damage in the retina and choroid around the 
arrays.
Histologic evaluations showed good preservation of the retina over 
the electrode array.
Conclusions: Implantation of a newly developed wide-field dual-
array STS retinal prosthesis into a scleral pocket of animals is 
surgically feasible and can be performed without significant damage 
to the retina or the animal. These findings indicate that it might be 
possible to implant more STS electrode arrays to cover a larger area 
of the retina to activate a larger visual field.
Commercial Relationships: Takeshi Morimoto, None; 
Hiroyuki Kanda, None; Tomomitsu Miyoshi; Takao Endo, 
None; Tibor K. Lohmann, None; Kohji Nishida, None; 
Takashi Fujikado, None
Program Number: 3720 Poster Board Number: D0181
Presentation Time: 11:00 AM–12:45 PM
Evaluation of the spatial resolution of electrode arrays for 
suprachoroidal retinal prosthesis by recording single-unit 
activities in the lateral geniculate nucleus
Hiroyuki Kanda1, Tomomitsu Miyoshi2, Takeshi Morimoto1, 
Takashi Fujikado1. 1Applied Visual Science, Osaka University 
Graduate School of Medicine, Suita, Japan; 2Integrative Physiology, 
Osaka University Graduate School of Medicine, Suita, Japan.
Purpose: To evaluate the spatial resolution of an electrode array for 
retinal prosthesis by suprachoroidal–transretinal stimulation (STS), 
we recorded the single-unit activities of relay cells in the lateral 
geniculate nucleus (LGN).
Methods: Implantation surgeries were performed in cats (n = 4) 
under general anesthesia. The electrode array was chronically 
implanted into the scleral pocket of eyes. The electrode array had the 
same specifications as that used in the 2nd generation device of STS 
retinal prosthesis. This electrode array comprised 49 bullet-shaped 
electrodes that were 0.5 mm in diameter and 0.3 mm in height. The 
center-to-center distance of the electrodes was 0.75 mm. Under 
general anesthesia, acute experiments for the evaluation of spatial 
resolution of the electrode array were performed in 2–4 weeks after 
the implantation surgeries. The electrode position was identified by 
optical coherence tomography. Charge-balanced biphasic pulses were 
applied (pulse duration, 0.5 mm; current intensity, 0.1–1.0 mA) to 
the retina via each electrode independently. Stimulating trials were 
repeated 10 or 40 times, and response probabilities of single-unit 
activities in LGN relay neurons were analyzed. Their receptive fields 
were identified by visual stimulation, and the relationship between 
response probabilities and distances from the center of the receptive 
fields to the stimulating sites were evaluated.
Results: The response probabilities decreased as the distance 
between the stimulating site and center of its receptive field 
increased. With 0.5 mA of stimulus intensity, the responsive area 
exhibiting a response probability of more than 50% was identified 
within a range of 1 mm from the stimulating site.
Conclusions: These findings demonstrate that this electrode array 
is able to achieve localized stimulation. Moreover, spatial resolution 
by the STS approach appears to be acceptable, although the distance 
between the electrode and retina in this approach is larger than that in 
epi- or sub-retinal approaches.
Commercial Relationships: Hiroyuki Kanda, NIDEK (P); 
Tomomitsu Miyoshi, None; Takeshi Morimoto, None; 
Takashi Fujikado, NIDEK (P)
Support: coordination, support and training program for 
transnational research, MEXT, Japan
Program Number: 3721 Poster Board Number: D0182
Presentation Time: 11:00 AM–12:45 PM
Spatio-temporal characteristics of retinal responses to subretinal 
photovoltaic stimulation
Richard Smith1, Elton Ho2, Georges A. Goetz2, 3, Xin Lei3, 
Theodore Kamins3, Jim Harris3, Keith Mathieson4, 
Daniel V. Palanker2, 5, Alexander Sher1. 1Santa Cruz Institute 
for Particle Physics, UC Santa Cruz, Santa Cruz, CA; 2Hansen 
Experimental Physics Lab, Stanford, Palo Alto, CA; 3Electrical 
Engineering, Stanford, Palo Alto, CA; 4Institute of Photonics, 
University of Strathclyde, Glasgow, United Kingdom; 
5Ophthalmology, Stanford, Palo Alto, CA.
Purpose: To measure the spatio-temporal receptive fields of the 
retinal ganglion cells activated via subretinal photovoltaic prostheses 
in degenerate and wild-type rat retinas, and compare them to the 
natural light responses in healthy retinas.
Methods: Activity of the RGCs was measured in-vitro with a 512 
channel multielectrode array. Photovoltaic array with 70µm pixels 
was placed on the photoreceptor side of healthy and degenerate 
(RCS) rat retinas. Prosthetic stimulation was performed with 880nm 
light pulsed at 20Hz and modulated by an LCD displaying binary 
white noise movies at frame rates of 10Hz and 20Hz. For stimulation 
of the healthy retina, the same LCD was used to display white noise 
movies at 30Hz frame rate with continuous visible light illumination. 
Spatio-temporal receptive fields of the RGCs were measured by 


Relative power consumption at the electrode-retina interface during retinal stimulation with voltage versus current controlled stimulus pulses

https://authors.library.caltech.edu/75477/1/Nimmagadda_2016p3718.pdf

Relative power consumption at the electrode-retina interface during retinal stimulation with voltage versus current controlled stimulus pulses

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