Development of a new visual prosthesis for preclinical studies on artificial vision

The technological evolution in materials science and microengineering favored the production of advanced visual prostheses useful for fighting blindness and to improve patients quality of life. Visual prostheses aim at replacing lost visual functions by artificial (electrical) stimulation of the remaining circuitry with microfabricated electrodes inducing phosphenes appearance in blind people. In particular, for people affected by retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration, retinal prostheses offer a valuable treatment option thanks to several advantages: among them, the retinotopic organization, the large surface area available for stimulation, and the straightforward surgical and optical access. The latter becomes very convenient for photovoltaic implants, in which amplified light entering the pupil is exploited as wireless source of power and visual information, allowing the implant to lay free-standing and the placement of a large number of stimulating pixels without the inconvenience of electrical connections. However, although all these advancements, there is nowadays no visual implant suited for artificial vision with both high spatial resolution and large visual field coverage. In this thesis, we developed a photovoltaic and foldable wide-field epiretinal prosthesis with a high density of stimulating pixels (more than 10400 and 18600 pixels with a density of 79 and 141 pixels/mm2, respectively) distributed over a very large surface area, covering 46 deg of visual field, greatly improved with respect to state-of-the-art implants. The large size of the implant imposes two major challenges: the necessity of a good contact between the implant and the retina and of a safe implantation procedure. To address these challenges, the photovoltaic interface is placed on a curved and stretchable substrate, able to be folded, injected into the eye through a small scleral cut, and self-unfold to recover the curvature matching the one of the eyes. Consequently, the rigid pixels were mechanically engineered to withstand the required deformation. We investigated the use of organic optoelectronic materials, such as P3HT:PCBM and PCPDTBT:PCBM, to manufacture photovoltaic pixels able to induce retinal ganglion cells activity upon illumination with short pulses of light. For both systems, light pulses of irradiances within the safety limits allowed the photogeneration of currents and voltages suitable for a stimulation frequency up to 20 Hz with green (565 nm) and near-infrared (730 nm) light, respectively. The conjugated polymer PEDOT:PSS and sputtered Ti (with TiN coating) were used for the anodic and cathodic ends correspondingly, with only the Ti-TiN surface exposed to the electrolytic solution. Ex vivo evaluation with blind mice retinas demonstrated that the photovoltaic pixels could induce, together with direct electrical short-latency stimulation, medium-latency spiking activity of retinal ganglion cells as evidence of prosthetic-induced network-mediated responses. Investigations and optimizations about functional, mechanical, thermal, optical, and stability properties of the prosthesis were carried out in vision of in vivo experiments with blind miniature pigs. Blinded by IAA treatment, the miniature pigs recovered light sensitivity when implanted with the prosthesis. This preliminary result motivates further preclinical inquiries with the prosthesis towards clinical applications.