Activation of retinal ganglion cells using a biomimetic artificial retina

Objective. Biomimetic protein-based artificial retinas offer a new paradigm for restoring vision for patients blinded by retinal degeneration. Artificial retinas, comprised of an ion-permeable membrane and alternating layers of bacteriorhodopsin (BR) and a polycation binder, are assembled using layer-by-layer (LBL) electrostatic adsorption. Upon light absorption, the oriented BR layers generate a unidirectional proton gradient. The main objective of this investigation is to demonstrate the ability of the ion-mediated subretinal artificial retina to activate retinal ganglion cells (RGCs) of degenerated retinal tissue. Approach. Ex vivo extracellular recording experiments with P23H line 1 rats are used to measure the response of RGCs following selective stimulation of our artificial retina using a pulsed light source. Single-unit recording is used to evaluate the efficiency and latency of activation, while a multielectrode array (MEA) is used to assess the spatial sensitivity of the artificial retina films. Main results. The activation efficiency of the artificial retina increases with increased incident light intensity and demonstrates an activation latency of ~150 ms. The results suggest that the implant is most efficient with 200 BR layers and can stimulate the retina using light intensities comparable to indoor ambient light. Results from using an MEA show that activation is limited to the targeted receptive field. Significance. The results of this study establish potential effectiveness of using an ion-mediated artificial retina to restore vision for those with degenerative retinal diseases, including retinitis pigmentosa (RP).

Photoelectric dye-based retinal prosthesis (OUReP) as a novel type of artificial retina

We have developed the world's first novel type of artificial retina, OUReP (Okayama University Retinal Prosthesis), in which a photoelectric dye that converts light energy into electric potential is covalently bonded to the surface of a polyethylene thin film as an insulator. The receptor that absorbs light and the output device that generates displacement current to stimulate nearby neurons are integrated in a sheet of thin film. It has become possible to measure the surface potential of the artificial retina OUReP using a Kelvin probe that measures the surface potential of semiconductors. When light is turned on and off to the artificial retina OUReP, the surface potential changes rapidly. As the light intensity is increased, the potential change on the surface of the artificial retina becomes larger. As for safety, the artificial retina OUReP was not toxic in all tests for biological evaluation of medical devices. As for efficacy, the artificial retina OUReP was implanted under the retina by vitreous surgery in monkey eyes which had chemically-induced macular degeneration with photoreceptor cell loss. Over the next 6 months, retinal detachment did not occur during the course, and the artificial retina was in contact with the retinal tissue. The amplitude of the visual evoked potential attenuated by macular degeneration recovered 1 month after implantation of the artificial retina, and the recovery of amplitude was maintained until 6 months after the implantation. By using multielectrode array-mounted dish recording system, it has been proved that action potential spikes are induced when the artificial retina is placed on degenerative retinal tissue of retinal dystrophic rats or mice and exposed to light, which is used as an index of the effectiveness of the artificial retina. We have established manufacturing and quality control of the device in a clean room facility, proved the safety and efficacy, and are preparing for first-in-human investigator-initiated clinical trials.

Colour-sensitive conjugated polymer inkjet-printed pixelated artificial retina model studied via a bio-hybrid photovoltaic device

In recent years, organic electronic materials have been shown to be a promising tool, even transplanted in vivo, for transducing light stimuli to non-functioning retinas. Here we developed a bio-hybrid optoelectronic device consisting of patterned organic polymer semiconductors interfaced with an electrolyte solution in a closed sandwich architecture in order to study the photo-response of photosensitive semiconducting layers or patterns in an environment imitating biological extracellular fluids. We demonstrate an artificial retina model composed of on an array of 42,100 pixels made of three different conjugated polymers via inkjet printing with 110 pixels/mm2 packing density. Photo-sensing through three-colour pixelation allows to resolve incoming light spectrally and spatially. The compact colour sensitive optoelectronic device represents an easy-to-handle photosensitive platform for the study of the photo response of artificial retina systems.