Optochemical retinal prosthesis for vision restoration

Current neural prostheses predominantly rely on electrical stimulation, which does not faithfully replicate the physiological mechanisms of synaptic transmission. Localized chemical delivery represents a more biomimetic strategy, yet previous approaches have been hindered by low spatial resolution, limited retention, and poor material biocompatibility and stability. This thesis investigates a planar solid-state platform for nanoscale, multisite neurotransmitter release, based on a nanopatterned membrane coupled to a reservoir. The system supports diffusion- and pressure-driven molecular translocation, enabling versatile delivery of glutamate and other compounds. We demonstrate that the device can reproducibly elicit glutamate-mediated neuronal activation in primary cultures, as well as in ex vivo mouse and non-human primate retinas. To achieve precise spatiotemporal control, a light-responsive nanovalve composed of a spiropyran-functionalized polymer was integrated into the device. This switchable barrier modulates pore permeability, blocking up to 96% of glutamate flux and enabling on-demand release at rates comparable to physiological synaptic transmission. The nanovalve exhibited excellent biocompatibility and successfully triggered functional responses in neurons and degenerated retinal explants, validating its potential as a biomimetic stimulation interface. A hybrid synapse between the device and target neurons was explored to achieve high spatial precision. Pre- and post-synaptic adhesion molecules were characterized, demonstrating synaptogenic activity in primary neurons. In parallel, an innovative subretinal injection platform integrating bioimpedance-guided feedback was developed to support precise viral delivery of these synaptic adhesion molecules. Applied to retinal degeneration, where photoreceptor loss in conditions such as retinitis pigmentosa and age-related macular degeneration remains irreversible, this technology offers a chemical alternative to gene therapy, optogenetics, or electronic prostheses. By combining light-controlled delivery with endogenous-like synaptic signaling, the proposed system establishes a foundation for next-generation neuroprosthetic strategies aimed at restoring vision and advancing brain–machine interfaces.