Project Summary Retinal degenerative diseases are the leading cause of irreversible vision loss. Current retina prosthesis are solid state implantable devices designed to stimulate sensation of vision in the eyes of individuals with these significant conditions. Resolution and pixel density are limited in the existing devices. In addition, these solid- state implants require invasive surgical incision and have risks and challenges post-op. New technologies and methods are still being sought for minimally invasive prostheses for precise and non-genetic retina stimulation. In this Trailblazer application, we propose an injectable optoacoustic retina prosthesis for high precision retina stimulation. The injectable prosthesis is a soft biocompatible optoacoustic material which can be injected in targeted areas in retina. Coupled with patterned illumination via a scanning strategy, the injectable retina prostheses are expected to achieve retinal stimulation with a spatial resolution of 40-50 µm. Such unprecedent injection strategy, ultra-high spatial precision, and potential of massive parallel capabilities, together with the soft and biocompatible design, offer clear advantages. A multi-disciplinary team with complementary expertise is assembled to perform the proposed activities. Prof. Chen Yang (PI) is an expert in nanomaterials and neural devices and interfaces for modulation and regeneration. Prof. Serge Picaud (Co-I, Institut de la Vision, France) has 30 years research experience in retina and vision. Our team has pioneered ultra-high precision optoacoustic neuromodulation. We have successfully shown the retina can be directly stimulated by optoacoustic. Our central hypothesis that via the design of the injectable optoacoustic retina prostheses, we will achieve minimally invasive retina stimulation at an unprecedented 50 micro-meter spatial precision. To test this central hypothesis, the following specific aims are proposed. In Aim 1 and 2, we will develop a highly efficient photoacoustic injectable biomaterial and demonstrate high precision retinal stimulation at micrometer-scale resolution by multi-electrode array recording of retinal tissues. In Aim 3, we will Evaluate the safety and efficacy of stimulation by injectable optoacoustic prostheses in rodent models. These efforts are expected to generate a conceptually new injectable prosthesis design offering massively parallel, high precision and genetics-free optoacoustic stimulation with translational potential to human.