HyVIS

Hybrid synapse for vision

01.06.2021 bis 31.05.2025

Degenerative diseases of the retina, such as Retinitis pigmentosa (RP) and age-related macular degeneration (AMD), hit light-sensitive photoreceptors and leave bipolar cells (BCs) deprived of light-dependent synaptic input. Neuronal degeneration starts affecting the presynaptic side of the synapse, while the denervated postsynaptic side preserves the ability to be activated. This project targets the recovery of the lost synaptic light-mediated input to BCs by artificially reproducing two of the key mechanisms involved in retinal image formation: glutamate release and high spatial resolution. BCs will be interfaced with plasmonic nanochannels filled with smart polymers able to release glutamate in response to optical stimuli, mimicking neurotransmitter release sites on presynaptic terminals. The functionalization of the nanochannels with appropriate adhesion molecules together with single cell genetic engineering will re-create the synaptic machinery and mediate contact formation between pre- and postsynaptic partners. No other attempts to recreate lost synapses by making an optically driven hybrid connection between a nano-sized eurotransmitter releasing device and the denervated postsynaptic cell have been attempted thus far. We propose stimulating neurons with a drastically novel method that surpasses the concept of electrical stimulation and that can go beyond single cell resolution to recreate lost synaptic connections with "hybrid nanosynapses". Moreover, the synergic combination of the proposed technologies paves the way for the breakthrough development of retinal prosthetics able to rescue the natural cell-specific connectivity of the inner retinal neurons.