HyVIS, an EU-funded initiative targeting degenerative eye diseasehas launched, with the aim of the four-year project to develop a way to restore sight in people with diseases such as age-related macular degeneration and retinitis pigmentosa, by restoring the photoreceptors’ sensitivity to light through a hybrid synapse. HyVIS (Hybrid synapse for VISion) has received €3 million ($3.39 million) under the EU’s Horizon 2020 research and innovation program. The HyVIS consortium is composed of six European institutions with expertise in material science, chemistry, physics, neuroscience, and medicine, and with a specific focus on nanotechnology and retina neurophysiology. The HyVIS research team will develop a retinal neuroprosthesis that will re-create synaptic connections in the retina. The technology will exploit residual neuronal functionality in the diseased retina to form hybrid synapses made from nanodevices and the retinal neurons that are no longer connected to the photoreceptors. The Italian Institute of Technology (IIT) is coordinating the project. Eindhoven University of Technology, the Institute of Molecular and Clinical Ophthalmology Basel, Sorbonne University, the University of Tübingen, and Maxwell Biosystems are partners in the project. “HyVIS will make it possible to restore the physiological activation of inner retinal neurons with very high spatial resolution,” project coordinator Elisabetta Colombo said. “The aim is to ensure that, in the presence of light, these neurons are activated with a resolution of more or less 5 mm, comparable to that achieved by the cones in the middle of the retina and responsible, in humans, for high-resolution vision.” By combining nanotechnology and optics, the HyVIS project will develop bionic synapses for retinal prostheses, designed to restore sight in people suffering from diseases such as retinitis pigmentosa and age-related macular degeneration. Courtesy of IIT-Istituto Italiano di Tecnologia. In experimental models of retinal degeneration, it has been shown that if a microinjection of glutamate, the primary excitatory neurotransmitter at the retinal level, is given underneath the retina, it is possible to stimulate the neurons. The researchers will incorporate this previously tested approach into their work on the hybrid synapse. The researchers will also capitalize on the demonstrated ability of hollow plasmonic nanochannels to enhance the electromagnetic field generated by light. They will use nanochannels to directly interact with the neurons at a nanoscale — the size range of synaptic clefts. Using both of these approaches, the researchers will interface the retinal bipolar cells with a plasmonic nanochannel filled with smart polymers that will release glutamate in response to optical stimuli, mimicking the physiological release process. In keeping with how a synapse is biologically created, the researchers will induce the postsynaptic specialization in the retina’s denervated bipolar cells by single-cell virus stamping, thereby sealing the synaptic connection. Presynaptic adhesion molecules coating the nanochannels and virus stamping will induce the denervated bipolar cells to express the receptors necessary to re-create the synaptic environment. The IIT Centre for Synaptic Neuroscience and Technologies and the Institute of Molecular and Clinical Ophthalmology Basel will provide facilities and knowledge of neuron cultures and retina explants and their interfacing with HyVIS synaptic device prototypes. IIT Plasmon Nanotechnologies will provide facilities for the optical and electrical design, fabrication, and characterization of 3D nanostructures for direct neuronal interfaces, the release of glutamate, and the integration of HyVIS prototypes. Eindhoven University of Technology will provide facilities for the synthetic organic chemistry, catalysis, and controlled polymerization experiments. The Institut de la Vision at Sorbonne University will provide facilities and knowledge on how to test the prototypes ex vivo with primate and rodent retinas. The Institute for Ophthalmic Research at the University of Tübingen will provide strategic and scientific input to ensure the success of product development and application. MaxWell Biosystems will provide technology, data analysis, and expertise related to electrophysiological in vitro testing of acute retinal preparations and retinal organoids.