Massively Parallel Optoacoustic Retinal Stimulation at Micrometer-Resolution

项目摘要 视网膜退行性疾病是不可逆视力丧失的主要原因。没有批准的医疗 这种干预可以治愈或逆转视网膜退行性疾病的进程。视网膜假体 设计用于刺激具有这些显著的视觉障碍的个体的眼睛中的视觉感觉的可植入装置。 条件然而，由于电流扩散，分辨率和像素密度在现有的电致发光器件中受到限制。 基于设备。新的技术和方法仍在寻求精确和非遗传植入 视网膜刺激，像素密度提高。在这个应用中，我们的目标是开发一个光声微- 透镜阵列（OAA）。该阵列可以生成用于大规模并行视网膜成像的聚焦超声的期望图案。 刺激具有40-50微米的焦点尺寸和高达178像素/mm 2的像素密度。如此超高的空间感 精确度、可变穿透力和大规模并行能力使我们能够专注于光声技术 而结合在软植入物设计中将提供优于现有方法的明显优点。一个多- 为执行拟议的活动，组建了具有互补专长的纪律小组。陈教授 Yang（PI）是纳米材料和开发新的神经接口的专家， 再生Fried教授（麻省总医院/哈佛医学院Co-I）具有相当的专业知识 研究视网膜和其他中枢神经系统神经元对电，磁和其他形式的人工刺激的反应。 刺激.程继新教授（合作者）是无标记化学成像和光声的专家 装置.我们的团队开创了超高精度的光声神经调制。我们已经成功 显示视网膜可以直接被光声刺激。这些可行性数据引出了我们的中心假设 通过光声透镜阵列的设计，光声能够提供大规模并行视网膜成像， 以前所未有的50微米空间精度进行刺激，为视网膜假体奠定基础。到 为了检验这一中心假设，提出了以下具体目标。在目标1中，我们将展示直接视网膜 通过膜片钳验证的TFOE以微米分辨率刺激四种亚型α RGC。在目标2中， 我们将使用多电子显微镜，通过OAA演示微米分辨率的大规模并行视网膜刺激。 阵列测量这些努力有望产生一种植入物设计， 高精度光声刺激作为无基因视网膜假体，具有向人类平移潜力。

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.