Towards High‐Acuity Vision Restoration: Hybrid Retinal Prosthesis Composed of a High‐Density Multielectrode Array Integrated With Glutamatergic Cells

Retinal prostheses offer a promising approach for vision restoring in patients with degenerative retinal diseases. However, current devices remain limited by their low spatial resolution, non‐selective retinal circuit activation, and unnatural pulsatile stimulation. To overcome these limitations, this work introduces a novel device in the form of a Hybrid Retinal Implant (HRI), composed of a high‐density electrode array integrated with glutamatergic neurons (human embryonic stem cell‐derived photoreceptor precursors, hESC‐PRPs). The electrodes are designed to create a tight neuron‐electrode coupling through a 3D microwell‐shaped design, thereby confining and amplifying the induced electric fields. Using finite element modeling, this work demonstrates a three‐order‐of‐magnitude reduction in activation threshold, reaching the picocoulomb (pC) level, while eliminating electrode crosstalk and enabling high‐resolution stimulation with a 10 µm pixel size. Moreover, in vitro studies confirm the significant reduction in activation charge threshold. Finally, implantation of the device in the subretinal space of rats with retinal degeneration reveals the survival of the hESC‐PRP cells within the microwells. Furthermore, the device‐integrated cells exhibit axonal sprouting toward the host bipolar cells and form putative synapses with the host retina. These results, therefore, suggest that the Hybrid Retinal Implant can restore vision with unparalleled visual acuity while closely mimicking natural vision.