Fig. 12.13  The average number of spikes elicited in two RGCs (a, b) as a function of stimulus charge. The responses of both cells increased with increased charge injection. While the response of the cell on the left (a) appeared to plateau with high charge injection, the response of the cell on the right (b) fell with high charge injection. Both cells were more sensitive to an anodal pulse. Reprinted from [54], Fig. 3, with permission

12.2.2.5  Dynamics of the Retinal Response

Stett et al. [53] found that the number of spikes in an evoked retinal response increased with increasing voltage level. In a later study [54], they reported that the number of spikes evoked per voltage pulse was almost a logarithmic function of the charge delivered (Fig. 12.13). This finding suggests that it may be possible to influence the intensity of a visual percept in a patient with a retinal prosthesis by adjusting the amplitude of the current pulses. Unfortunately, further increases in the injected charge eventually led to a decrease in the number of spikes for some cells (Fig. 12.13b).

12.2.2.6  Comparing Subvs. Epiretinal Stimulation

It is difficult to draw definitive conclusions from the existing studies that compare the thresholds elicited by subvs. epiretinal stimulation. O’Hearn et al. [36] measured thresholds in the mouse retina using two 125 mm disk electrodes (bipolar configuration) and 1 ms duration biphasic pulses (cathodal first). Thresholds for epiretinal stimulation were 30 mA (0.61 mC/cm2) while thresholds for subretinal stimulation were 77 mA (1.57 mC/cm2) suggesting that epiretinal stimulation is more effective (Table 12.1).

248 S.I. Fried and R.J. Jensen

Table 12.1  Comparison of subvs. epiretinal thresholds

O’Hearn et al. (125 mm diameter electrode, biphasic pulses)

Jensen et al. (500 mm diameter electrode)

The results of two different Jensen et al. studies [19, 25] can also be used to compare thresholds. Both studies used identical stimulation parameters, including a 500 mm stimulating electrode and pulse durations of 0.1 and 2.0 ms and were restricted to OFF RGCs of the rabbit retina. The thresholds in response to epiretinal stimulation were lower than those from subretinal stimulation for both pulse durations tested (0.1 and 2.0 ms); however the difference was small for 2.0 ms pulses. While these results are qualitatively in agreement with O’Hearn et al., Jensen and Rizzo point out that it may be more accurate to compare epiretinal cathodal pulses to subretinal anodal pulses since in both cases current flows through the retina in the same direction [19]. Under these conditions, subretinal thresholds are significantly lower with both short and long pulses (Table 12.1, bottom, compare columns I and III).

It is difficult to assess the discrepancies between the O’Hearn et al. and Jensen and Rizzo studies. Both the stimulus waveform and electrode size are different between studies and either (or both) may contribute to threshold differences. In addition, the O’Hearn study was unable to distinguish between the early and late phase responses and therefore comparison with the Jensen et al. studies may not be appropriate. In addition, neither group was able to ascertain whether photoreceptors were activated by stimulation raising the possibility that the differences arise because different neurons were activated in each study. Further research is needed to better understand the relative thresholds and underlying mechanism differences between suband epiretinal stimulation.

12.3  Electrophysiological Properties of RGCs

in Degenerate Retina

Electrophysiological studies on RGCs in degenerate retina have been made in the rd1 mouse and the dystrophic Royal College of Surgeons (RCS) rat. Similar to a form of retinitis pigmentosa (RP) in humans, the rd1 mouse has a mutation in the gene for the b-subunit of cGMP phosphodiesterase-6 [7]. As a consequence, rapid rod photoreceptor degeneration begins at approximately postnatal day (P)10, with nearly all photoreceptors lost by P36 [3]. The RCS rat has a mutation in the receptor