Hybrid optogenetic and electrical stimulation of retinal ganglion cells for artificial vision.

Abstract

Millions of adults worldwide experience severe visual impairment due to photoreceptor loss from retinal diseases such as retinitis pigmentosa and macular degeneration. Retinal prostheses that provide artificial vision by stimulating the surviving retinal ganglion cells (RGCs) have emerged as a promising therapy. However, all clinically approved retinal prostheses that use electrical stimulation face the issue of electrical spread. As such, the quality of restored vision provided by existing devices has been limited. Optogenetic approaches provide greater spatial precision, however, they have poor temporal properties compared to electrical stimulation.

We developed an opto-electrical hybrid approach and surveyed this stimulation strategy in the retina of two animal models: normal-sighted transgenic mice that express ChR2-H134R in a sub-population of RGCs and the degenerated retina of Royal College of Surgeons rats with residual RGCs transduced with ChrimsonR. We conducted whole-cell patch clamp recordings and measured calcium transients with the biosensor GCaMP7s to determine single-cell and population responses to hybrid stimulation, respectively.

Hybrid stimulation reduced both electrical and optogenetic activation thresholds. Optical thresholds could be halved with electrical supplementation and synergistically, the opto-electrical coupling reduced the electrical intensity requirements to elicit action potentials by ∼50 % (p < 0.0001). Additionally, hybrid stimulation evoked significantly higher firing frequencies, by an order of up to 2×, when compared to electrical or optical-only methods (p < 0.0001). These properties of hybrid stimulation were replicated in the diseased retina, where the reduced activation thresholds contributed to significantly reduced spread of activation compared to electrical stimulation alone (p < 0.05), a challenge that persists in devices that utilize extracellular electrical stimulation. Hybrid stimulation improved the spatial resolution of RGC activation when applied at retina-electrode spacing reflective of current epiretinal and suprachoroidal devices.

Combining the optogenetic and electrical modes of activation enabled significant reductions of each component in the stimulus, leading to more localised stimulation when compared to electrical-only stimulation, while also reducing the optical intensity required for optogenetic activation. Together with improvements in response reliability, hybrid stimulation may not only improve the resolution and refresh rate of future visual prostheses but may also provide greater control in neuromodulation for any bionic device that interfaces with neural tissue.