Prosthetic strategies for visual restoration based on semiconducting polymeric nanoparticles

Neurodegenerative diseases lead to the irreversible death of neuronal cells, particularly affecting individuals in advanced age. Advances in neurotechnologies and bioengineering are therefore crucial for developing tools to counteract or restore the loss of function resulting from these conditions. Finding an instrument capable of effectively stimulating neurons is a challenge that many research groups are currently addressing. We will address the two main retinal dystrophies suffering from lack of effective treatments as targets of this technology: retinitis pigmentosa and age-related macular degeneration. We also discuss current retinal prosthetic strategies and associated problems, such as low spatial resolution, limited retinal coverage, and a lack of selective and physiological stimulation of inner retinal pathways. We propose a prototype for a neuronal stimulation prosthesis made of a liquid suspension of nanoparticles of the photoexcitable polymer Poly-3-HexylThiophene-2,5-diyl (P3HT), widely used in the production of solar cells. Given the promising results that P3HT has shown in previous in vitro and in vivo studies, our main objective is to use P3HT nanoparticles as a liquid retinal prosthesis for end-stage animal models of retinal degeneration. Our results show that a single subretinal injection of P3HT nanoparticles can effectively restore lost visual functionalities in blind animals with different types of photoreceptor degenerations caused by distinct mutations in genes expressed by the retinal pigment epithelium (Royal College of Surgeons rats) and photoreceptors (rd10 mice). We also explored the application of this technology for the direct neuronal stimulation of the primary visual cortex. Through light-cue classical conditioning and two-photon microscopy experiments, we demonstrate that photostimulation of nanoparticles injected into the primary visual cortex can evoke a response, which can elicit a visual percept. In conclusion, we present a proof of concept utilizing P3HT nanoparticles as a prototype for neuronal stimulation, with broader applications for the light-mediated reactivation and stimulation of areas in which neuronal transmission has been compromised by neurodegeneration.