From 2D to 3D Flexible Intraretinal Implants—Towards a New Generation of Visual Prostheses

The development of visual prostheses that stimulate the retina electrically has allowed significant advances toward the restoration of useful vision in the daily life of blind patients with retinal degenerative diseases. Nonetheless, such improvements are still rudimentary and the efficiency of retinal implants did not meet the expectations of patients, to the point that commercially available retinal implants were withdrawn recently from the market [1]. To further develop the field of retinal-based visual prosthetics, it is of vital importance to better understand the physiology of healthy and diseased retinas and to improve the efficiency of retinal implants upon electrical stimulation. To this end, feedback about electrical activity in the retina is desirable. Given the above, our research consortium has proposed the development of a bidirectional communication strategy. The idea is that the implant comes in close contact with vital neurons inside the retina to perform simultaneous electrical stimulation and recording of the retina. It thereby allows optimization and acknowledgment of the efficiency of the electrical stimulation process for the restoration of vision.<br/>To this end, we developed a bidirectional microelectrode array (BiMEA), comprising flexible (parylene-C-based) penetrating multi-shank and multi-site neural probes for retinal applications with iridium oxide or PEDOT: PSS electrodes [2-4]. 2D intraretinal probes were first developed, allowing an <i>in vitro</i> proof of concept with explanted rodent retinas that showed the feasibility of an intraretinal bidirectional prosthetic device. Here, we showed the capability of intraretinal recording while capturing distinct neuronal responses upon electrical stimulation on both, healthy and diseased retinas. Excitatory and inhibitory, as well as monotonic, non-monotonic, and saturated neural responses were captured when charges between 0.2 nC – 2.5 nC were applied.<br/>Furthermore, our devices showed a small acute insertion footprint in explanted retinas when using miniaturized probes (7 µm-thick, 50 µm-wide, and 140/180 µm-long), thereby reducing the acute insertion trauma area by 2-fold when compared to silicon Michigan-like arrays (20 µm-thick, 60 µm-wide, 312 µm-long). Moving even one step forward, we designed, developed, and tested <i>in vitro </i>3D flexible penetrating retinal implants for the first time. The latter allowed the recording of physiological responses of light-adapted retinas. Paving the way toward <i>in vivo</i> applications, intraretinal probes were validated in cadaveric animal models, exposing the feasibility of implanting such probes with an open-sky surgery for a future acute <i>in vivo</i> validation of the BiMEA concept.<br/>References:<br/>[1] Ayton, L. N. <i>et al.</i> An update on retinal prostheses. <i>Clin. Neurophysiol.</i> <b>131</b>, 1383–1398 (2020).<br/>[2] Rincón Montes, V. <i>et al.</i> Toward a bidirectional communication between retinal cells and a prosthetic device - A proof of concept. <i>Front. Neurosci.</i> <b>13</b>, 1–19 (2019).<br/>[3] Rincón Montes, V. <i>et al.</i> Development and in vitro validation of flexible intraretinal probes. <i>Sci. Rep.</i> <b>10</b>, 1–14 (2020).<br/>[4] Rincón Montes, V. Development, characterization, and application of intraretinal implants. (RWTH Aachen University, 2021).