RETINO2

We aim to develop of a new kind of artificial retina containing pixellized architectures of vertically aligned TiO2-based nanotubes, acting as artificial photoreceptors in replacement of degenerated natural ones, when the ‘smart’ neuronal network of retina is partially maintain-ned, as in the case of ca. 50% of blindness in developed countries. The patient number world-wide concerned ranges from 200,000 when considering only a class of rare diseases such as retinitis pigmentosa, to several millions, when including only part of those affected with age-related macular degeneration. This confers a first-order societal interest to this research area. The retinal prosthesis concept with external electrical stimulation of partially-persistent neuronal network, has been implemented so far with implanted parts located both inside and outside of the eyeball, for authorizing information and/or energy transfer to the electro-des. Even if clinical trials validated the concept, with restoration of some visual perception to implanted patients, models tested till now do not allow for a useful vision, i.e. for assuring motion autonomy, face recognition and reading ability (beyond large letter recognition). Our strategy would lead to single implantation of a photoreceptive matrix inside eyeball, with no need of passing a cable through the eye wall. Originality and novelty turn are based on the use of a semi-conductor material made of TiO2 single oxide, nanostructured as pixelli-zed vertically aligned nanotube architecture, obtained by electrochemical anodic synthesis, and carefully modified for transferring its light absorption to the visible range and thus obtaining an architecturized material photoresponsive to visible light stimulation. Prior to the project, the concept of artificial retina based on TiO2 photosensors allowing neuronal stimulation and the feasibility of the controlled and tunable photosensor pixellization, have been validated by the partners. A resolution of at least to 1000 pixels, necessary for restoring useful vision, will be reached by setting a micro-machining process allowing µ-etching by laser ablation of aligned TiO2 nanotube continuous coating, followed by inter-pixel isolating filling obtained by laser-induced local mineralization of a precursor mineral ink, both processes being industrialized by one of the partners. The ease-of-use of both µ-machining processes, associated to their cutting accuracy, to their automatized servo-control and low costs, will allow the symbolic level of 1000 pixels to be reached, while maintaining low implant production costs. The artificial retina device efficiency will be first validated by in vitro electrophysiology over cultured cells and dystrophic retinas. The functional testing will be carried out for assessing sensitivity gain for subretinally implanted blind rats, via the histology of the implant/retina contact and the results of behavior testing. Our results should lead to the consortium enlargement by including a Center for Clinical Investigations, to set the basis for a future clinical testing of this new kind of artificial retina.