Toward a Bidirectional Communication Between Retinal Cells and a Prosthetic Device – A Proof of Concept

Abstract

Background: Significant progress toward the recovery of useful vision in blind patients with severe degenerative retinal diseases caused by photoreceptor death has been achieved with the development of visual prostheses that stimulate the retina electrically. However, currently used prostheses do not provide feedback about the retinal activity before and upon stimulation and do not adjust to changes during the remodeling processes in the retina. Both features are desirable to improve the efficiency of the electrical stimulation (ES) therapy offered by these devices. Accordingly, devices that not only enable ES but at the same time provide information about the retinal activity are beneficial. Given the above, a bidirectional communication strategy, in which inner retinal cells are stimulated and the output neurons of the retina, the ganglion cells, are recorded using penetrating microelectrode arrays (MEAs) is proposed. Methods: Custom-made penetrating MEAs with four silicon-based shanks, each one with three or four iridium oxide electrodes specifically designed to match retinal dimensions were used to record the activity of light-adapted wildtype mice retinas and degenerated retinas from rd10 mice in vitro. In addition, responses to high potassium concentration and to light stimulation in wildtype retinas were examined. Furthermore, voltage-controlled ES was performed. Results: The spiking activity of retinal ganglion cells (RGCs) was recorded at different depths of penetration inside the retina. Physiological responses during an increase of the extracellular potassium concentration and phasic and tonic responses during light stimulation were captured. Moreover, pathologic rhythmic activity was recorded from degenerated retinas. Finally, ES of the inner retina and simultaneous recording of the activity of RGCs was accomplished. Conclusion: The access to different layers of the retina with penetrating electrodes while recording at the same time the spiking activity of RGCs broadens the use and the

Electrophysiological investigation of intact retina with soft printed organic neural interface

“…In humans, stimulation efficiency relies on patient reports and acuity tests. For better understanding the retina intrinsic activity and for achieving efficient stimulation, the best stimulation parameters must be identified in the eye [45,50]. Achieving bi-directional stimulation, as well as high resolution electrodes in retinal prosthesis, will help in identifying effective, cell-specific stimulation.…”

Toward the Next Generation of Neural Iontronic Interfaces

“…[123,124] For fundamental studies, explanted retinae are interfaced with planar or penetrating microelectrode arrays to study their activity and the most optimal electrical and optoelectronic stimulation protocols. [51,125,126] Thereby, transparent substrates for the microelectrode arrays are of high interest. It is also known that during typical neurodegeneration processes in the eye such as Retinitis Pigmentosa or age-related macula degeneration, the neural networks undergo morphological as well as functional reorganization and the state of degeneration is strongly specific to the individual patient.…”

“…In high‐density microelectrode arrays, which commonly rely on CMOS technologies and switch matrices for selecting a specific subset of electrodes, [ 20 ] the substrate inevitably becomes opaque, making the combination of electrical and optical methods more challenging. For more invasive recordings, for instance from retinal neurons, [ 51,52 ] organoids, [ 53 ] thicker brain slices, or intact brain tissue, [ 54 ] penetrating electrode configurations are used in which a shank, a needle, or other sharp structure can be inserted into the tissue to access neurons in deeper regions. Such technologies are commonly used in sparse configurations, such as the UTAH array, [ 23 ] but high‐density electrode configurations, such as Neuropixels arrays [ 18,24,55 ] have recently become more widespread and are likely to become the standard in future applications.…”

Advances in visual prostheses: engineering and biological challenges

“…Similar to other neuromodulation therapies [194], researchers are also considering and exploring bi-directional and closed-loop feedback approaches for retinal [36,[195][196][197][198] and cortical [100,199] prostheses. This combination would allow prostheses to automatically adjust the stimulation parameters and improve the performance over time.…”