High frequency stimulations of wild type and blind mouse retinas using titanium dioxide nanotubes as artificial photoreceptors

Abstract

Purpose : Artificial retinas are a concrete hope to restore sight to blind patients, notably those affected with retinitis pigmentosa. However, present architectures are costly to produce, while the restored visual acuity remains below the legal threshold for blindness. Alternative approaches, based on nanomaterials or organic films, are being increasingly explored. We have focused our interest on titanium dioxide (TiO₂), an inexpensive and biocompatible photovoltaic material, and more specifically on aligned TiO₂ nanotubes, to determine if they can be used as artificial photoreceptors.

Methods : Films of vertically aligned TiO₂ nanotubes were synthesized by electrochemical anodization of either a titanium foil or of a thin layer of titanium sputtered on FTO glass. Surface depolarizations in response to light flashes (near-UV and white light) were measured by positioning a patch-clamp electrode in contact with the nanotubes. Flatmount retinas of WT or rhodopsin^P23H mutant mice (a model of retinitis pigmentosa) were put in contact with the nanotubes, photoreceptor-side down, and ganglion cell activity recorded in loose-patch mode.

Results : Nanotubes responds to near-UV light with considerably larger depolarizarions (~x15) than nanoparticules, for comparable thickness (2-5 µm). Those obtained from sputtered titanium displayed smaller, slower but more stable surface depolarizations than those synthesized from a titanium foil. When the TiO₂ nanotube films were placed in contact with photoreceptors (WT mouse retina) or directly with bipolar cells (rhodopsin^P23H mouse retina), short and small light spots (5-20 ms, 50-100 µm diameter) evoked an intensity-dependent, reproducible spiking output in ganglion cells, with a short response latency, for stimulation frequencies up to 25 Hz.

Conclusions : TiO₂ nanotubes constitute a promising alternative for artificial retina applications. Ganglion cell activity could be driven at high frequency with near-UV light but not with visible light. Consequently, we aim to shift the sensitivity of TiO₂ nanotubes towards visible light by loading with other semiconducting metal oxides or sulfides particles, and/or co-doping of TiO₂. Having a continuous rather than a discrete array of electrodes should allow a fine tuning of the prosthetic stimulations, through modulation of the spot size, duration and precise localization over the implant surface.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.