CNS*2020 Online

Wei Tong, Michael R Ibbotson, Hamish Meffin

Retinal prostheses can restore visual sensations in people that have lost their photoreceptors by electrically stimulating surviving retinal ganglion cells (RGCs). Currently, there are mainly three types of retinal prostheses under development, based on their implantation locations: epi-retinal, sub- retinal and suprachoroidal [1]. Clinical studies from all three types of devices indicate that, although a sense of vision can be restored, the visual acuity obtained is limited and functional vision, such as navigation and facial recognition remains challenging. One major difficulty is associated with the low spatial resolution obtained from electrical stimulation, i.e. the large spread of activation amongst RGCs leads to blurred or distorted visual percepts. Particularly, with epi-retinal implants, experiments have revealed that the leading cause of widespread activation is the unintended activation of passing RGC axons, which lead to elongated phosphines in patients [2].

This work proposes to use rectangular electrodes oriented parallel to the axon bundles to prevent the activation of passing axon bundles. Here, we first used simulation to investigate the interaction of neural tissue orientation and stimulation electrode configuration on the RGC activation patterns. A four-layer computational model of epiretinal extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue was applied, as previously described [3], using a volume conductor model known as the cellular composite model. As shown in Figure 1a, our model shows that stimulating with rectangular electrode aligned with the nerve fiber layer (i.e. passing axon bundles), can be used to achieve selective activation of axon initial segments, rather than passing fibers.

The simulation results were then confirmed with experiments. Here, data were acquired from adult Long Evan rats and by recording the response of RGCs from whole-mount retina preparations using calcium imaging. Electrical stimulation was delivered through a diamond coated carbon fiber electrode with a length of 200 µm and diameter of 10 µm. The electrode was placed either parallel or perpendicular to the RGC axon bundles. Biphasic stimuli with different pulse durations of 33-500 µs were tested. Our experimental observations (Figure 1b) are consistent with the expectations of the simulations, and the use of rectangular electrodes placed parallel to axon bundles can significantly reduce the activation of RGC axon bundles. When using biphasic stimulation as short as 33 µs, the activated RGCs were mostly confined to the region below or very close-to the electrode, as observed using confocal microscopy.

To conclude, this work provides a stimulation strategy for reducing the spread of RGC activation for epi-retinal prostheses. Using ultrashort pulses together with rectangular electrodes parallel to the RGC axon bundles, the performance of epi-retinal prostheses will be improved significantly, thus promising to restore a higher quality of vision to the blind.

References

[1] J. D. Weiland et al, _Annual Review of Vision Science, Vol 2,_ vol. 2, pp. 273-294, 2016.

[2] D. Nanduri et al, _Investigative ophthalmology & visual science,_ vol. 53, no. 1, pp. 205-214, 2012.

[3] T. B. Esler, et al, _PloS one,_ vol. 13, no. 3, pp. e0193598, 2018.