Selective Activation of Retinal Ganglion Cell Subtypes Through Targeted Electrical Stimulation Parameters.

To restore vision to the low vision, epiretinal implants have been developed to electrically stimulate the healthy retinal ganglion cells (RGCs) in the degenerate retina. Given the diversity of retinal ganglion cells as well as the difference in their visual function, selective activation of RGCs subtypes can significantly improve the quality of the restored vision. Our recent results demonstrated that with the proper modulation of the current amplitude, small D1-bistratified cells with the contribution to blue/yellow color opponent pathway can be selectively activated at high frequency (200 Hz). The computational results correlated with the clinical findings revealing the blue sensation of 5/7 subjects with epiretinal implants at high frequency. Here we further explored the impacts of alterations in pulse duration and interphase gap on the response of RGCs at high frequency. We used the developed RGCs, A2-monostratified and D1-bistratified, and examined their response to a range of pulse durations (0.1-1.2 ms) and interphase gaps (0-1 ms). We found that the use of short pulse durations with no interphase gap at high frequency increases the differential response of RGCs, offering better opportunities for selective activation of D1 cells. The presence of the interphase gap has shown to reduce the overall differential response of RGCs. We also explored how the low density of calcium channels enhances the responsiveness of RGCs at high frequency.