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Yossi Mandel, Amos Markus, Gal Shpun, Revital Schick, Yoav Chemla, Itai Henn, Nairouz Farah; Hybrid Retina: A Novel Concept for Sight Restoration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3974.
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© ARVO (1962-2015); The Authors (2016-present)
To overcome the large neuron-electrode distance and the non-selective activation of various retinal pathways (e.g. ON and OFF) 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 electrical stimulation of the implant 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, by a combination of IWR1e, SAG, CHIR99021 in agarose microwells. COMSOL Multyphysics 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 we employed calcium imaging (rhod2) to visualize intracellular calcium dynamics in response to electrical activation. Finally, optimization and characterization of the neuron-electrode interface were performed by advanced imaging techniques, on electrode arrays which were fabricated by our group.
Cell differentiation efficiency was over 80%, as shown by Fluorescence-activated cell sorting to the photoreceptor 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 the 3-150 fold increase in the expression of sodium, potassium and calcium voltage-sensitive channels at 12w of differentiation in addition to evidence of voltage-dependent currents observed in voltage clamp recordings. A marked increase and decrease in intracellular calcium was observed following cathodic and anodic electrical pulses, respectively. Finally, surface treatment of electrodes with RGD resulted in a two-fold increase in electrode-neural cells growth area and decreased the electrode-neuron cleft, as revealed by scanning electrode and focused ion beam microscopy.
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 vision at high resolution and quality .
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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