DOI: https://doi.org/10.29363/nanoge.neuronics.2024.030
Publication date: 18th December 2023
Vision restoration in patients with outer retinal degenerative diseases, such as Age-related Macular Degeneration and Retinitis Pigmentosa can be achieved by bypassing the degenerated photoreceptors and the electrical stimulation of the relatively well-preserved inner retina through electrode implants. Although current retinal prostheses have been shown to provide useful vision in blind patients, the obtained visual acuity and quality are still relatively low, because of inherent limitations of current retinal prosthetic technologies: long electrodes-neuron distance with increased current activation threshold and non-selective neural activation. We are developing a novel approach to overcome these limitations by a hybrid retinal composed of a high-density electrode array (pixel distance down to the cellular size of 10µm), where each electrode is coupled with a glutamatergic neuron to create a tight neuron-electrode coupling. Following implantation of the hybrid prosthesis, the glutamatergic neurons integrate and synapse with the host retinal circuits. Patterned electrical stimulation of these glutamatergic neurons by the electrodes modulates glutamate release onto the synapse with the host bipolar cells after which the remaining retinal circuitry is activated identically to natural vision while keeping high resolution and selective retinal cells activation. We have shown that hESC-derived photoreceptor precursors create glutamatergic synapses in-vitro; the cells can be activated by the electric field, as was shown with patch-clamp and calcium imaging. Confocal imaging revealed that the cell created a tight-seal configuration within the micro-well device. Following implantation to the subretinal space of rats with retinal degeneration, the precursors survived for over a month; the cells show axonal elongation to the inner retina. This presentation will further discuss various challenges, design considerations and potential solutions and approaches toward the development of a hybrid retinal implant.
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