R41EY035609

Retinal degeneration involving progressive deterioration and loss of function of photoreceptors is a major cause of permanent vision loss worldwide. Strategies to treat these incurable conditions incorporate retinal prostheses via electrically stimulating surviving retinal neurons with implanted devices in the eye, optogenetic therapy, and sonogenetic therapy. Existing challenges of these strategies include invasive manner, complex implantation surgeries, and risky gene therapy. Therefore, an approach that can apply directly to the naturally existing mechanoreceptors to recover visual function in blind patients is desired. For this purpose, several pioneer studies have explored the feasibility of US stimulation of the retina to potentially evoke neuron activities [1–4]. However, the lack of in vivo demonstration of vision restoration and potential pattern generation from retinal degenerative models at a high spatiotemporal resolution impeded the role of US stimulation as an efficient vision restoration approach. To move beyond these limitations, in our recent study [5], we demonstrated US as a promising approach to induce neuron activities in the Royal College of Surgeons (RCS) rat in vivo, a retinal degenerative animal model widely used for assessing therapeutic effects. Based on our previous successful demonstration, we are developing a novel wearable array for ultrasound stimulation on the retina. It should be noted that our new device is an upgraded version of previous works. Specifically, in this proposal, we are going to engineer, design, and fabricate a prototype of our device for technology validation, reliability, and functionality assessments. This device will consist of an image acquisition unit to capture the visual scenes, an image processing unit to convert visual scenes into ultrasonic stimulation patterns, and a racing ring lens ultrasound transducer array that generates patterned stimulation on the retina. The transducer is flexible and placed outside the eyeball, similar to the application of a contact lens. Ultrasound emitted from the transducer can reach the retina without passing through the lens, thus greatly minimizing the acoustic absorption in the lens. Ultimately, we hope our findings demonstrate that ultrasound stimulation of the retina is a safe and effective approach with a high spatiotemporal resolution, indicating a promising future of ultrasound stimulation as a novel and noninvasive visual prosthesis for translational applications in blind patients.