Abstract: PURPOSE: Photoreceptor degeneration is the main cause of blindness in retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. The objective of this study is to assess the performance of Au@TiO_2-x nanowire arrays as artificial photoreceptors to restore primary visual function in blind mice and non-human primates with photoreceptor degeneration.
METHODS: To evaluate the improvement in visual temporal and spatial resolution in blind mice, Au@TiO_2-x nanowire arrays were assessed using in vitro patch-clamp recordings and mouse behavior paradigm based on 2AFC. Long-term continuous monitoring of light-induced responses in the visual cortex neurons of blind mice after implantation of nanowire arrays was conducted using two-photon calcium imaging technology. The safety, stability, and light-responsive capabilities of monkeys implanted with nanowire arrays were examined through fundus imaging, OCT imaging, and visually guided saccade behavior experiments, respectively.
RESULTS: Subretinal implantation of nanowire arrays in blind mice was capable of detecting drifting gratings and flashing objects at low light intensity thresholds (15.70 - 18.09 μW·mm^-2), with spatial and temporal resolutions of 77.5 μm and 3.92 Hz, respectively. Additionally, long-term in vivo calcium imaging suggested plastic changes in visual cortical circuits after nanowire implant. The nanowire arrays exhibited good biocompatibility and stability for 54 weeks after subretinal implantation in monkeys, capable of detecting light stimuli of 0.5º in diameter at 10 μW·mm^-2 in visually guided saccade experiments.
CONCLUSIONS: Our findings demonstrate the potential of Au@TiO_2-x nanowire array as artificial photoreceptors to ameliorate visual deficits in patients with photoreceptor degeneration.

Key words: Retina, Artificial photoreceptors, Retinal prosthesis, Nanowire array