Massively Parallel Optoacoustic Retinal Stimulation at Micrometer-Resolution

Project Summary Retinal degenerative diseases are the leading cause of irreversible vision loss. There is no approved medical intervention that could cure or reverse the courses of retinal degenerative diseases. Retina prosthesis are implantable devices designed to stimulate sensation of vision in the eyes of individuals with these significant conditions. Yet, due to the current spreading, resolution and pixel density are limited in the existing electrical based devices. New technologies and methods are still being sought for precise and non-genetic implantable retinal stimulation with an improved pixel density. In this application, we aim to develop an optoacoustic micro- lens array (OAA). This array can generate a desired pattern of focus ultrasound for massively parallel retinal stimulation with a focus size of 40-50 microns and pixel density up to 178 pixels per mm2. Such ultra-high spatial precision, variable penetration and massive parallel capabilities enabled our focused optoacoustic technology while incorporated in the soft implant design will offer clear advantages over existing methods. A multi- disciplinary team with complementary expertise is assembled to perform the proposed activities. Prof. Chen Yang (PI) is an expert in nanomaterials and development of new neural interface for modulation and regeneration. Prof. Fried (Co-I, Mass General Hospital/Harvard Medical School) has considerable expertise studying the responses of retinal and other CNS neurons to electric, magnetic, and other forms of artificial stimulation. Prof. Ji-Xin Cheng (collaborator) is an expert in label-free chemical imaging and photoacoustic devices. Our team has pioneered ultra-high precision optoacoustic neuromodulation. We have successfully shown the retina can directly be stimulated by optoacoustic. These feasibility data led to our central hypothesis that via the design of the optoacoustic lens arrays, optoacoustic is able to deliver massively parallel retinal stimulation at an unprecedented 50 micro-meter spatial precision, serving a foundation for retinal prothesis. To test this central hypothesis, the following specific aims are proposed. In Aim 1, we will demonstrate direct retinal stimulation of four subtypes alpha RGC at micrometer-resolution by TFOE validated by patch clamp. In Aim 2, we will demonstrate massively parallel retinal stimulation at micrometer resolution by OAA using multi-electron array measurements. These efforts are expected to generate an implant design offering massively parallel and high precision optoacoustic stimulation as genetics-free retinal prosthesis with translational potential to human.