Hybrid Retinal Prosthesis for Restoration of Sight

Yossi Mandel 1,2 Nairouz Farah 1 Gal Shpun 2,3 Amos Markus 1 Revital Shick 1 Yoav Chemla 1,2 Itai Henn 1,2
1Faculty of Life Sciences, Bar-Ilan, Israel
2Bar-Ilan Institute for Nanotechnology and Advanced Material Science, Israel
3Bar-Ilan, Israel

To overcome the large neuron-electrode distance and the non-selective activation retinal circuits, which limit the efficiency of currently available retinal prostheses, we propose a novel approach based on coupling glutamatergic neuron to high-density electrode arrays, which we term Hybrid Retinal Prosthesis. The coupled cells will synapse with the host retina and induce the activation of retinal circuitry at a cellular resolution with visual restoration at high acuity.

We generated photoreceptor precursors from human embryonic stem cells, to serve as glutamatergic neurons. COMSOL Multiphysics computer modeling was utilized to evaluate and optimize the effect of various geometrical parameters on neurons activation charge. To electro-physiologically characterize the generated cells and study the electrode-neural interface we employed both patch-clamp and calcium imaging technique.

Cell differentiation efficiency was over 80%, as shown by staining to the photoreceptor precursor marker CRX. Simulations revealed that charge thresholds could be reduced to 0.03nC in a configuration where neurons are sealed in a microwell, as compared to 49nC in a flat electrode configuration. Maturation of neurons was demonstrated by significant increase in the expression of various voltage-gated ionic channels. A marked increase and decrease in intracellular calcium were observed in response to electrical activation. FIB imaging revealed tight neural interface with the micro-well structure.

We propose a new strategy for vision restoration with a hybrid retinal implant composed of a high-density electrode array incorporated with glutamatergic neurons. The hybrid device has the potential to mimic many features of natural vision and restore high resolution and quality sight.

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