INJECTABLE PHOTOACTIVE DEVICES FOR RETINAL PROSTHESIS: DESIGN, SYNTHESIS AND TESTING OF POLYMER-BASED NANOPARTICLES

The past three decades have witnessed tremendous research to bridge the gap between simulated and natural vision. With a fair share of breakthroughs and challenges, visual restorative therapy continues to fuel interest amongst the scientific community globally. Age-related macular degeneration and Retinitis pigmentosa are among the top untreatable, chronic neurodegenerative eye diseases responsible for debilitating lives of millions of people. Different therapeutic methods have been investigated including gene replacement, optogenetics, stem cell therapy, and electronic retinal prostheses, among which the latter holds the longest development period. Subretinal retinal approaches have shown encouraging results for a partial enhancement in vision acquired by targeting the residual inner retinal neurons, exploiting various stimulation mechanisms. Notwithstanding the scientific community's efforts in enhancing a suitable retinal restorative stimulation tool, surgical invasiveness, and genetic modification still represent a bottleneck in the field of retinal degeneration therapies, together with the inability to provide high-resolution vision. Over recent years, significant advancements have been achieved in retinal prosthetics, primarily driven by the shift from inorganic to organic devices that utilize conjugated polymers. A potential breakthrough involves the development of injectable conjugated polymeric nanoparticles serving as a "liquid" retinal prosthesis. This thesis aims to explore a prospective enhancement of the "liquid" retinal concept by incorporating graphene to a novel co-polymeric formulation of the previously developed injectable nanoparticles. It outlines the design and fabrication of P3HT:PCBM nanoparticles with graphenic core via the nanoprecipitation method. The comprehensive evaluation of physical properties confirms the formation of a reproducible, stable, and fairly monodisperse population. In vitro viability experiments on primary neuronal cultures and ex vivo multi-electrode recordings from dystrophic retinal explants show good biocompatibility of the nanoparticles, localization on the cell membrane without internalization over time, and increased firing modulation of retinal neurons upon illumination. These results overall suggest that graphene could be successfully embedded in nanoparticles of photovoltaic polymers and represents a potential new strategy for the development of an injectable light-sensitive neurostimulation tool.