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1From The Center for Innovative Visual Rehabilitation, VA Medical Center, Boston, Massachusetts; the 2Department of Ophthalmology, Harvard Medical School and the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and the 3Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
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Abstract |
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METHODS. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100-µs duration were delivered to the inner surface of the retina from a 5-µm long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used.
RESULTS. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one half) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds.
CONCLUSIONS. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation.
Stimulation possibilities are either epiretinal (the stimulating points are on the inner surface of the retina) or subretinal (the stimulating points are on the outer surface of the retina, between the neural retina and the underlying pigment epithelium). The goal of the present study was to determine current threshold and increase in threshold with electrode displacement for epiretinal stimulation of retinal ganglion cells. The former can be used to judge the power requirements of a functioning prosthesis and the potential for electrochemical toxicity that occurs as current passes through the metal electrode. The latter can be used to guide the choice of interelectrode spacing and estimate the potential spatial resolution that could be derived from a prosthesis. Another motivation is the desire to achieve selective stimulation of ganglion cell bodies rather than axons en passage, which would presumably enhance the quality of perceptions induced by a retinal prosthesis.
Only a few studies6 7 8 have been reported in which the currents needed to stimulate individual ganglion cells in the retina with an epiretinal electrode were investigated, and in none of these studies was the current thresholds of axons compared with cell bodies or the current thresholds measured as a function of electrode distance from the site of activation. Also, with the exception of Grumet et al.,8 relatively large microelectrodes have been used in these studies. A small microelectrode was used in the present study to enable a more precise study of threshold variation with electrode position near a cell body or axon of a ganglion cell.
Preliminary portions of this work have been presented elsewhere9 (Wyatt JL, et al. IOVS 1994;35:ARVO Abstract 593; Rizzo JF, et al. IOVS 1997;38:ARVO Abstract 182).
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Retinal Preparation
The rabbits were sedated by an intraperitoneal injection of urethane (1.6 g/kg) and then received an intravenous injection of pentobarbital sodium (20 mg/kg) for deep anesthesia. Under normal room lighting, an eye was enucleated and hemisected, and the vitreous humor was removed with gentle suction applied to the back of a Pasteur pipet. A strip (
1 x 2 cm) of inferior retina and attached sclera including the optic nerve head was removed and laid flat, ganglion cell side up, on a 10° inclined platform. The retinal strip was superfused with a solution of 8.9 g/L Ames medium (Sigma-Aldrich, St. Louis, MO), 1.9 g/L NaHCO3, and 0.8 g/L D-glucose and saturated with 95% O2-5% CO2. The solution flowed by gravity over the surface of the retina at a rate of 1.4 to 1.7 mL/min. The temperature of the solution on the retina was maintained at 34°C to 36°C. Diffuse background light (1 µW/cm2 at the retina) was present throughout the experiments.
Electrical Recording and Stimulation
Extracellular potentials were recorded from ganglion cell axons by using standard glass-insulated tungsten microelectrodes.10 Single-unit activity was amplified with a differential amplifier (DAM 80; World Precision Instruments, Sarasota, FL) with cutoff frequencies of 300 Hz and 10 kHz and displayed on an analog oscilloscope. The indifferent electrode was a 22-gauge needle electrically grounded to the retinal preparation.
The stimulating electrode was made of platinum and iridium with an exposed tip approximately 5 µm in length and 2 µm in diameter at the base (FHC Inc., Bowdoinham, ME; cat. 30-05-1). The small electrode area, smaller than one would perhaps expect to use in a prosthesis, enables a more precise study of threshold variation with electrode position near a cell body or axon. For stability, the shaft of the platinum-iridium electrode was surrounded by and glued to a concentric glass tube that extended to a point 6 mm short of the tip of the electrode. All stimuli in this study were monophasic, 100-µs duration, square-wave cathodal or anodal current pulses. The current pulses were generated by a calibrated stimulator (model S88; Grass Telefactor, Inc., W. Warwick, RI) and photoelectric stimulus isolation unit (model PSIU6; Grass Telefactor). The return electrode was a Ag-AgCl sheet (surface area: 1.2 cm2) that lay on a platform beneath the sclera.
General Experimental Protocol
The recording microelectrode was mounted on a micromanipulator and the microelectrode tip positioned above the retina several millimeters inferior to the optic nerve head. While lowering the microelectrode tip toward the surface of the retina, the experimenter intermittently stimulated the retina with light from a hand-held flashlight. Once action potentials from a single axon were isolated from background activity, the receptive field center of the ganglion cell was sought by flashing across the retina a 300-µm spot of light that was generated by an optical system described elsewhere.11 After the center of the receptive field was located, the cell was physiologically categorized primarily on the basis of its response to flashes of light.11 To simplify data analysis, only recordings from off-center, brisk-transient ganglion cells were selected for study. In addition, to avoid having the stimulus artifact (produced by the stimulating current) obscure the displayed evoked action potentials, only cells with receptive fields at least 6 mm from the recording electrode were studied.
Because the retinal strip lay on a 10° inclined platform, a 10° wedge was attached to the bottom of a second micromanipulator that held the stimulating electrode. This alignment insured that the plane of motion of the stimulating electrode tip matched the plane of the retinal surface. The x, y, and z spatial coordinates of the stimulating electrode were measured from three vernier micrometers on the micromanipulator.
Stimulation thresholds were determined by increasing a subthreshold current until action potentials were elicited more than 50% of the time over 10 or more consecutive stimulations. To aid detection of orthodromically generated action potentials, the oscilloscope sweep was pretriggered from the stimulator (Grass Telefactor). With few exceptions, only one ganglion cell was studied in each retinal strip. To minimize damage to the electrodes, currents greater than 300 µA were generally not used. The ability of the electrodes to pass current was routinely checked during the course of the study.
In some experiments, to block synaptic transmission within the retina, 1 mM cadmium chloride (CdCl2; Sigma-Aldrich) was added to the bathing medium from a syringe pump, as described previously.11
Specific Experimental Protocol
Stimulation Near the Cell Body.
With the spot of light centered within the receptive field, the tip of the stimulating electrode was lowered in the bathing medium and positioned in the center of the spot. Alignment of the stimulating electrode over the receptive field center was facilitated by imaging with a video camera and displaying a 12x magnified view of the retina on a monitor. The spot was turned off and monophasic, square-wave current pulses (100 µs in duration, applied at 4–5 Hz) were delivered through the stimulating electrode. Stimulus current was continually adjusted as the electrode was slowly lowered toward the retina, and the physical point at which the threshold ceased to decline was taken to be the retinal surface.
In the search for the point of lowest threshold within the receptive field center, threshold measurements were first made along a line parallel to the y-axis extending ±150 µm from the center of the receptive field (Fig. 1) . From the lowest threshold point found, a further search for the minimum was made along a line extending ±150 µm parallel to the x-axis. From this second minimum threshold point, a final search was conducted ±50 µm along a new line parallel to the y-axis. The point of lowest threshold found in the final search was used as the "measured origin," and all other electrode positions were plotted in relation to it. This tripartite search strategy was performed by using cathodal stimulation for half of the cells (n = 10) and anodal search for the other half (n = 10). Once the measured origin was determined for one polarity, the threshold to the opposite polarity was immediately determined without moving the electrode.
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Much more dense measurements of current thresholds were made for one cell, for which the measured origin was found in an identical manner. In this case, 100 measurements were made at 25-µm increments in a 10 x 10 array in the x-y plane from the lowest threshold point found with anodal search. At all points, threshold-to-anodal current was first determined and then threshold to opposite polarity was immediately measured without moving the electrode.
Stimulation Near the Axon.
To study axonal thresholds, the tip of a stimulating electrode was positioned at least 1.5 mm from the center of a ganglion cell’s receptive field along an imaginary line connecting that center and the optic nerve head. Thresholds along axons were always studied below the visual streak, where axons are unmyelinated.
In the search for the point of lowest threshold, threshold measurements were first made along a line parallel to the y-axis (i.e., along a line perpendicular to the presumed course of the axon) extending ±150 µm. The point of lowest threshold was used as the measured origin, and all other electrode positions were plotted in relation to it. This search strategy was performed by using cathodal stimulation in 9 cells and anodal in 10 other cells. Once the measured origin was determined for one polarity, the threshold to the opposite polarity was immediately determined without moving the electrode. Thresholds at the retinal surface were then measured for six additional points separated by 50 µm along the x-axis and then six points along the y-axis. After each threshold determination, the microelectrode was raised 150 to 200 µm before attempting to reposition it for the next measurement. Finally, change in threshold as a function of distance above the measured origin (i.e., the z-axis) was determined by measuring thresholds 25, 50, 75, 100, and 150 µm above the retina.
Statistical Methods
Medians (rather than means) are used to report data, primarily because they are much less sensitive to the effect of a small number of extreme outlying values. Medians are also helpful whenever high thresholds are reported as being simply greater than a certain value, as was done whenever it was judged that further elevation of current might damage the electrodes or cells. With such occasional semiquantitative results, medians but not means can still be accurately calculated.
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Minimal Absolute Thresholds
Stimulation Near the Cell Body.
Thresholds at the measured origin (see the Methods section for definition) within the receptive fields of 20 ganglion cells were plotted (Fig. 2A) . In 10 cells, the measured origin was found with cathodal current pulses and in the other 10 with anodal current pulses. Thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the measured origin. Median thresholds were lowest when the same polarity was used for search and stimulation. This was especially true of cathodal stimulation (median threshold obtained with cathodal search was one fourteenth that obtained with anodal search). Polarity-matched cathodal search and stimulation produced a narrow range of minimum thresholds (0.26–0.85 µA) with a median that was one tenth (0.50 vs. 5.0 µA) that of polarity-matched anodal search and stimulation.
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Dense, Two-Dimensional Array of Threshold Measurements
Stimulation Near the Cell Body.
A dense, two-dimensional array of threshold measurements in one ganglion cell, stimulated within the center of its receptive field, illustrates the dependence of threshold pattern on stimulus polarity (Fig. 3) . This single difference in method produced an obviously lower and more highly localized minimum threshold for cathodal stimulation. Cathodal stimulation produced the lowest (0.18 µA) and highest (110 µA) thresholds.
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Thresholds along the x-, y-, and z-Axes
Stimulation Near the Cell Body.
Thresholds along the x-, y-, and z-axes in the 20 cells in Figure 2A were segregated by polarity of stimulation (Fig. 4A) . The large spread in thresholds around the median was evident from the individual data, which were referenced to the linear axis. The semilog axis, in which vertical differences correspond to ratios of thresholds, expanded the lower range of thresholds and made evident the percentage increase in threshold with distance from the measured origin. The semilog plots emphasize the lower minimums and steeper percentage increase in thresholds around the measured origin with cathodal stimulation along the x- and y-axes. Recall from Figure 1 that the positive x-axis extended from the measured origin toward the optic nerve head, along the presumed path of the axon. The asymmetry of cathodal thresholds along the x-axis presumably resulted from stimulation of axons along the positive x-axis (Fig. 1) .
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Polarity of the Search Method
Stimulation Near the Cell Body.
Figure 5A shows the data in Figure 4A separated by the polarity of the search method. For most positions of the stimulating electrode, thresholds were lower when the search and stimulation were polarity matched. Also, the lowest threshold in the vicinity of each cell body was found at the point revealed by the initial search to be the lowest threshold (i.e., the measured origin) when polarity-matched search and stimulation methods were used. This was not always true when the search and stimulation were of opposite polarity. The pairing between search and stimulation methods also had an effect on thresholds away from the measured origin. For polarity-matched methods, a 100-µm displacement of the electrode from the measured origin resulted in substantially greater relative increases in threshold for cathodal–cathodal than for anodal–anodal search and stimulation along all three axes. Similar to the more aggregated data in Figure 4A , the polarity-matched median threshold profiles along the x-axis were relatively symmetric with anodal, but not with cathodal, stimulation. This asymmetry results from the relatively slower increase in cathodal threshold from the measured origin to (+)150 µm, along the presumed axonal path (positive x-axis). Aggregated and polarity-matched cathodal methods both showed a deeper valley of thresholds around the measured origin along the x- and y-axes than the corresponding anodal method. Details of threshold increase with displacement are in Table 1 .
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Stimulation Near the Axon.
Figure 5B shows the separation of the data in Figure 4B by polarity of search method. The effect of search method was neither consistent nor dramatic. Matched search and stimulation yielded lower median thresholds in 14 of the 19 different electrode measurement sites with anodal stimulation, but in only 6 sites with cathodal stimulation. (Thresholds at the measured origin were determined once for the x- and y-axis plots and then redetermined for the z-axis plots.) For every axon, the lowest threshold turned out to lay either at the measured origin or along the x-axis. Details of threshold increase with electrode displacement are in Table 2 .
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Power Fit to the Threshold Data
One simple hypothesis is that the electric field diminishes with the square of distance from the electrode during stimulation, as occurs in a uniform electrically linear medium with distant boundaries, and that thresholds increase accordingly. The hypothesis would imply, if true, that I = kr2. The current threshold (I) rises as the square of distance (r). The coefficient k characterizes the spread of the stimulating current. To compare the data with this hypothesis, we first normalized each measured threshold current, dividing it by the threshold measured for the same cell or axon at a 100-µm displacement in the same direction with the same stimulus polarity. (Only data obtained with search and stimulation of matching polarity were used. Data were excluded for electrode displacements along an axon (i.e., in the positive and negative x directions for axonal stimulation and in the positive x direction for cell body stimulation). Displacements in the positive and negative y directions were lumped into a single category.)
The normalized thresholds were plotted and compared with square-law growth, which appears as a straight line on the log–log scale used. As a typical example, the normalized thresholds for anodal axon stimulation with electrode displacements in the z direction (i.e., upward from the retinal surface) are plotted in Figure 6 . Median thresholds fell less rapidly at displacements of 50 µm and lower from the measured origin than at larger displacements in Figure 6 , and also in 7 other of the 10 categories shown in Figure 7 . (The two exceptions were anodal thresholds in the y direction for both cell bodies and axons.) For this reason we considered only the growth in threshold of displacements greater than 50 µm. The dashed line in Figure 6 , corresponding to growth as the 1.78 power of displacement, gives the best fit on this log–log plot to the normalized thresholds for all displacements greater than 50 µm. (By "best fit," we mean the straight line on the log–log plot passing through unity at 100 µm that minimizes the sum of the squared differences between the logs of normalized thresholds at 75 and 150 µm and the log values on the straight line.) The advantage of fitting to the logarithm is that it gives equal weight to equal percentage deviations from square-law growth at 75 and 150 µm, despite the typically larger thresholds at the larger displacement.
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Effects of Cadmium Chloride
In this study, we found that electrical stimuli near threshold almost always evoked a single action potential, which was rigidly time locked to the electrical stimulus. Furthermore, there was a sharp stimulus threshold. Together, these findings indicate that the cells were directly stimulated. However, to be certain of this, for some cells we examined the thresholds to electrical stimulation when synaptic transmission in the retina was blocked. To block synaptic transmission, we applied 1 mM cadmium chloride in the bath for 5 minutes, which was a more than adequate time to abolish light responses from the ganglion cells. Thresholds were then remeasured without moving the stimulating electrode. Data were collected on 11 cells: In 8 cells, thresholds were measured with the stimulating electrode placed near the ganglion cell body; in the other 3 cells, thresholds were measured with the stimulating electrode placed near the axon. In no case did cadmium chloride abolish the electrically evoked action potentials. In six of the eight cells in which the stimulating electrode was placed near the cell body, the threshold current was elevated 11% to 23%. In one cell the threshold current remained unchanged, and in the other the threshold current decreased 32%. In all three cells in which the stimulating electrode was placed near the axon, the threshold current was elevated 8% to 35%. We attribute the small shifts in threshold to the direct, nonspecific effects of cadmium chloride.
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Minimal Absolute Thresholds
As summarized in Figure 2 , both cell bodies and axons are more sensitive to cathodal stimulation than anodal stimulation. This finding was not unexpected; it has long been known that cathodal currents are more effective than anodal currents in stimulating neurons within the central nervous system.18 19 20 Figure 2 also shows that the minimum absolute threshold for cell body stimulation was dependent on the polarity of current used to search for the minimum threshold point. This was particularly true of thresholds obtained with cathodal stimulation—the median threshold after cathodal search was approximately 14 times lower (0.50 vs. 7.2 µA) than the median threshold after anodal search. In comparison, the median threshold for cathodal stimulation of axons after cathodal search was virtually the same (0.94 vs. 0.95 µA) as that after anodal search. Why should the polarity of current used to search for the minimum threshold point matter in cell bodies but not in axons?
On the one hand, cathodal stimulation of any excitable cell is readily explained by direct depolarization of the cell in the region under the electrode. Anodal stimulation, on the other hand, results in hyperpolarization of the cell in the region under the electrode. To explain anodal stimulation it has been proposed that current leaves (and depolarizes) sites distant from the electrode.15 Consequently, the site of lowest threshold for anodal stimulation may be different from the site of lowest threshold for cathodal stimulation. This was clearly the case when a dense, two-dimensional array of threshold measurements was made near the cell body of one ganglion cell (Fig. 3) . For this cell, the measured origin was located using anodal search and the site of lowest threshold for cathodal stimulation was located approximately 150 µm from the measured origin. Whereas a retinal ganglion cell has a complex geometry in the area of its receptive field, an intraretinal axon is essentially a uniform, one-dimensional structure. Consequently, the point of minimum threshold of an axon is not a single point but a series of points along its length. Whether the region of depolarization is under the electrode (cathodal stimulation) or at a site distant from the electrode (anodal stimulation) should be inconsequential in locating a minimum threshold point.
Another finding from the data presented in Figure 2 is that with matched-polarity cathodal search and stimulation, the median threshold for cell body stimulation was approximately one half (0.50 vs. 0.94 µA) that of axonal stimulation when the stimulating electrode was at the measured origin. With matched-polarity anodal search and stimulation, the median threshold for cell body stimulation was nearly the same as that of axonal stimulation (5.0 vs. 6.5 µA). Thus, with cathodal current, it appears possible to stimulate cell bodies preferentially. That is, if an electrode is placed on an arbitrary patch of retina containing axons and cell bodies, cells with initial segments that are directly under the electrode will be activated first. It is noteworthy that several years ago Greenberg et al.21 had predicted based on a computational model of electrical stimulation of retinal ganglion cells that it should be possible to stimulate retinal ganglion cells electrically near the cell body at lower thresholds than at the axon.
Thresholds along the x-, y-, and z-Axes
Median cathodal thresholds were lower than median anodal thresholds in both cell bodies and axons at almost every displacement (Figs. 4 5) . Median axonal thresholds increased more rapidly with displacement in the y and z directions under cathodal stimulation than under anodal stimulation (Fig. 4B) . Similar behavior was noted in cell bodies (Fig. 4A) . We also found that with matched-polarity cathodal search and stimulation, median axonal thresholds generally increased less steeply with displacement than cell body thresholds. (The one slight exception being z-axis thresholds at 100 µm.) With matched-polarity anodal search and stimulation, however, no consistent difference in steepness between cell bodies and axons was found (Tables 1 2) .
We found that the median axonal thresholds scarcely changed with displacement in x-axis under either cathodal or anodal stimulation (Figs. 4B 5B , Table 2 ). This finding is reassuring from a technical standpoint because this axis presumably lies along the path of the axon. The median cell body thresholds did not increase as steeply along the positive x-axis as it did along the negative x-axis (Figs. 4A 5A) . In most ganglion cells, the axon would have presumably coursed along the positive x-axis.
For application to a retinal prosthesis, two important points to be made are that both cell bodies and axons are more sensitive to cathodal than to anodal stimulation, even at distances far removed from the point of lowest threshold, and that cathodal current should provide a more focal stimulation of the retina.
Polarity of the Search Method
The search polarity had little effect on axonal thresholds at most displacements in distinct contrast to the cell body’s great sensitivity to search polarity (Fig. 5) . This finding suggests that the location of the measured origin is more or less independent of the search method for an axon, whereas this is not true for the cell body.
Power Fit to the Threshold Data
The threshold for electrical stimulation of neurons with an extracellular microelectrode has generally been considered to vary with the square of the distance between the neuron and the electrode tip (see review by Tehovnik22 ). We found though that the threshold’s increase with distance is not accurately described by a radius (r)-squared law. A best fit to the data gives a power law ranging from r0.84 to r3.19 (Fig. 7) . Thresholds declined more slowly than r2 as distance was reduced from 50 to 25 µm (e.g., Fig. 6 ). No systematic difference was found between the exponents for axons and cell bodies. A mathematical model to explain why our data cannot be described by a radius-squared law is currently being developed in our laboratory.
Comparison with Previous Studies
Although the retina has been electrically stimulated in several studies, we are aware of only three studies6 7 8 in which the minimum currents needed to activate individual retinal ganglion cells with an epiretinal electrode have been investigated. The first study, by Crapper and Noell,6 recorded the responses of rabbit retinal ganglion cells to electrical stimuli (0.5-ms cathodal and anodal pulses) delivered from a 100-µm steel needle electrode. They found that ganglion cells produce one or more bursts of action potentials on electrical stimulation. They supposed that photoreceptors, not ganglion cells, are the primary site of activation for the burst of action potentials. They also mentioned that with a strong electrical stimulus an "immediate" response could be seen, which they attributed to direct stimulation of ganglion cells. In contrast to their findings, we found that the threshold current for direct stimulation of ganglion cells is lower than that needed to generate a delayed burst of spikes at the 100-µs duration we used. Bursts of spikes were observed with currents considerably above the threshold for direct stimulation (Jensen RJ, unpublished observations, 2001). We believe this difference in our findings and theirs may be due to the differences in the electrode size and pulse duration.23
Humayun et al.7 stimulated the inner retinal surface of rabbits and bullfrogs with biphasic current pulses (75-µs phase duration) from a relatively large (200-µm diameter) spherical electrode. They found that responses were recordable in ganglion cells with currents as low as 50 µA. The responses exhibited a short latency, suggesting direct stimulation of the ganglion cells. That they needed approximately 100 times more current to activate a ganglion cell is not surprising because of the large size of the electrode and hence the reduced charge density. They did not report observing bursts of spikes at longer latencies, which is not surprising because they used a short pulse duration in their study. Short pulse durations appear to be ineffective in activating preganglionic neurons in frog24 and rabbit retinas.23
Grumet et al.8 stimulated rabbit retinal ganglion cells with biphasic current pulses from a microelectrode array of 10-µm-diameter disc electrodes. They reported that threshold currents in the cells in their study were all below 2 µA with axonal stimulation. In our study, we found that the threshold currents with axonal stimulation were all below the 3.2 µA with monophasic cathodal stimulation (Fig. 2) . Such close agreement between their results and ours is probably due to the relatively similar size of electrodes in both studies, although the surface area of their disc electrode (79 µm2) is approximately five times the surface area of our cone-shaped electrode (16 µm2). Because of limitations in their experimental setup, they were not able to investigate the amount of current needed to stimulate a ganglion cell near its cell body, and therefore no comparisons can be made for cell body stimulation.
Applicability of Results to a Retinal Prosthesis
The electrodes used had an exposed area that was conical in shape: 5 µm long and 2 µm in diameter at the base. These small electrodes were chosen to give a more accurate indication of threshold variation with displacement near a cell body or axon than could be obtained with the much larger electrodes typically considered for a retinal implant (e.g., 400-µm-diameter discs).25 26 The small size resulted in an average charge density of 0.63 millicoulombs/cm2 for a 1-µA, 100-µs pulse, which is near the maximum charge density recommended for safe prolonged stimulation (e.g., 2–4 mC/cm2 for iridium oxide27 and 0.3–0.4 mC/cm2 for platinum28 ). At 100 µm displacement, the charge density at median threshold would exceed the upper limit for iridium oxide. Furthermore, because current is known to concentrate at the tip of such pointed electrodes, the peak charge density is doubtless greater by an unknown amount.
It is reassuring that similarly low-current thresholds are obtained for rabbit retinal ganglion cell axons with 10-µm-diameter disc electrodes,8 which presumably produce a charge density at least five times less than our electrode. It remains to be determined whether ganglion cell bodies have a lower threshold to cathodal stimulation with these disc electrodes, as we have found in the present study with our cone-shaped microelectrode.
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Footnotes |
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Submitted for publication October 9, 2002; revised March 4, 2003; accepted March 10, 2003.
Disclosure: R.J. Jensen, None; J.F. Rizzo III, None; O.R. Ziv, None; A. Grumet, None; J. Wyatt, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C. 
1734 solely to indicate this fact.
Corresponding author: Ralph J. Jensen, The Center for Innovative Visual Rehabilitation, VA Medical Center, Mail Stop 151E, 150 South Huntington Avenue, Boston, MA 02130; ralph.jensen{at}med.va.gov.
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