Hybrid synapse for vision

Project Information

HyVIS

Grant agreement ID: 964468

DOI

10.3030/964468

Project closed

EC signature date 20 January 2021

Start date 1 June 2021

End date 31 May 2026

Funded under

• EXCELLENT SCIENCE - Future and Emerging Technologies (FET)

Total cost

€ 2 935 302,50

EU contribution

€ 2 935 302,50

Coordinated by

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
Italy

Periodic Reporting for period 2 - HyVIS (Hybrid synapse for vision)

Reporting period: 2022-06-01 to 2023-11-30

Summary of the context and overall objectives of the project

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 to stimulate neurons with a drastically novel method that can go beyond single cell resolution to recreate lost synaptic connections with "hybrid nanosynapses": surviving retinal neurons will be interfaced with plasmonic nanochannels filled with smart polymers able to release neurotrasmitter in response to optical stimuli.
The main objectives of the project are i) the fabrication of the hybrid synapse and ii) the light-mediated stimulation of primary neurons, retinal explants and retina organoids.
The revolutionary retinal neuroprosthesis may not only improve the life quality of people affected by retinal degeneration diseases, but also have a significant impact on public healthcare systems and society economy.

The HyVIS team succeded in engineering, fabricating and testing the prototypes of retinal prosthesis for a "chemical" stimulation of primary and retinal neurons. Novel photosentive moieties have been synthetized to release neurotransmitter on demand upon illumination, capitalizing on a change of hydrophobicity. Finally, the molecular constructs and virus necessary for a targeted stimulation of retinal neurons have been produced and tested in vitro on cell lines. The next and last part of our project will be focussing on the assembly of the while device and its testing on retinal explants from mice and non-human primates and retinal organoids.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The HyVIS first prototype composed of a thin silicon nitride membrane etched into a Si wafer frame decorated with nanostructures have been successfully designed, fabricated and distributed among the consortium. Stimulus-responsive polymers have been engineered and their characterization ongoing. The biocompatibility studies of the prototypes in vitro demonstrate no interference of the materials and architectures with the viability of the neuronal networks. Early ex vivo evaluations on retinal explants are ongoing together with the engineering of the proper holders to fit the prototypes to the microscopes layouts. Retinal organoids were also developed to be ready for testing with the first prototypes.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Sight is our paramount sense, and the new concepts and technological advancements in the field of retina prosthetics, such as those of HyVIS innovation, may not only improve the life quality of people affected by retinal degeneration diseases, but also have a significant impact on public healthcare systems and society economy. Moreover, HyVIS will have a strong transformational impact in: (i) computational neuroscience and ophthalmology, for an artificial device able to drive formation of new neural-like hybrid circuits; (ii) material science and engineering, for the applicability of the acquired technical advancements to other fields (e.g. computer science, electronics and robotics); (iii) nanochemistry, nanomedicine and neurosciences, for the application to novel nanoscale drug delivery systems and brain prostheses.

Schematic representation of the hybrid synapse machinery