Current retinal prostheses have been shown to provide useful vision in blind patients by direct electrical activation of the inner retinal neurons. However, inherent limitations of direct neuronal activation (lack of proximity and non-selective neuronal activation), make it challenging to achieve full restoration of vision. We propose an out-of-the-box approach toward sight restoration with a hybrid retinal prosthesis composed of a high-density electrode array (pixel distance down to the cellular size of 10- 5µm), where each individual 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 in an identical manner to natural vision. The ultimate electrode-neurons proximity and the low charge neural activation threshold should enable the significant reduction in electrode dimensions and an increase in pixel density as well as the continuous graded potential activation, similarly to the bipolar and photoreceptor cells while the indirect activation of the host retina by glutamatergic neurons, can potentially preserve the natural visual circuits (e.g. ON and OFF).
In this talk I will present our results with generation of photoreceptor precursors from hESC. I will present the functional characterization of these cells by path-clamp and calcium imaging techniques, which demonstrated that the intracellular calcium of the cells can be electrically modified. I will further discuss the many challenges and approaches taken in device fabrication and tissue engineering toward the development of hybrid retinal prosthesis.