High Resolution Optoelectronic Retinal Prosthesis

描述（由申请人提供）：在发达国家，无法治愈的失明的两个主要原因是视网膜色素变性（RP）和终末期黄斑变性（AMD）。 虽然这些疾病的病因各不相同，但它们有一个共同的结果，即光感受器（视网膜的感光细胞）的变性。 恢复视觉功能的一种方法是使用将视觉信息编码为电信号的视网膜假体来刺激剩余的视网膜回路。 面临的挑战是设计这样一个系统，与患病的视网膜接口，并提供视觉环境的高分辨率表示。 该项目汇集了工程师，神经生物学家和眼科医生的独特组合，以完成专门设计用于实现视觉功能水平的高分辨率视网膜假体系统的开发和评估。 在这个系统中，处理后的图像的视觉场景被投射到视网膜下放置的微光电二极管阵列的脉冲红外光。 阵列中的光伏像素将脉冲光转换成直接刺激视网膜神经元的双相电流脉冲。 这种光电视网膜假体系统提供了几个新颖和有利的特点：植入物中的数百或数千个像素可以被同时和独立地激活，简化的外科手术，用户可调节的图像处理，高分辨率刺激，眼睛运动和图像感知之间的自然联系，促进神经元与刺激电极紧密接近的三维植入物结构，以及允许扩展刺激场的植入物的模块化设计。 这种多功能系统可用于解决RP和AMD患者的不同需求。 大部分系统组件已经开发，并测试了一些方面。 原型光电二极管阵列显示出长期的生物相容性，并在用IR闪光灯照明时提供视网膜刺激。 该提案代表了在临床试验之前，在RP的大鼠和猫模型中系统开发的最后两个阶段。 拟定实验将评估：电生理和行为实验中平面和三维植入物的刺激有效性和安全限值、长期生物相容性以及空间分辨率限值。 公共卫生相关性：在发达国家，无法治愈的失明的两个主要原因是视网膜色素变性（RP）和终末期年龄相关性黄斑变性（AMD）。 这两种疾病都会导致光感受器的丧失，而视网膜中的大部分信号处理神经元都被保留下来。 我们建议通过光伏视网膜下假体使用高分辨率电刺激将视觉信息传递到神经视网膜中的剩余细胞来恢复盲人的视力。 这种光电系统代表了一种创新的多功能设计，可满足RP和AMD患者的不同需求。

DESCRIPTION (provided by applicant): The two leading causes of untreatable blindness in the developed world are retinitis pigmentosa (RP) and end-stage macular degeneration (AMD). While the etiology of the diseases varies, they share a common outcome, the degeneration of photoreceptors, the light sensing cells of the retina. One approach to restoring visual function is to stimulate the remaining retinal circuitry using a retinal prosthetic that encodes the visual information into electrical signals. The challenge is to design such a system that interfaces with the diseased retina and provides a high resolution representation of the visual environment. This project brings together a unique combination of engineers, neurobiologists, and ophthalmologists to complete the development and evaluation of a high-resolution retinal prosthetic system designed specifically to achieve functional levels of vision. In this system the processed images of the visual scene are projected by pulsed infrared light onto a subretinally placed microphotodiode array. Photovoltaic pixels in the array convert pulsed light into biphasic pulses of electric current that directly stimulate retinal neurons. This Optoelectronic Retinal Prosthetic System offers several novel and advantageous features: hundreds or thousands of pixels in the implant can be activated simultaneously and independently, simplified surgical procedure, user-adjustable image processing, high resolution stimulation, a natural link between eye movements and image perception, a 3- dimensional implant structure that facilitates close proximity of neurons with stimulating electrodes, and modular design of the implant that allows for expansion of the stimulated field. Such a versatile system could be used to address the divergent needs of RP and AMD patients. Most of the system components have been developed and some aspects tested. Prototype photodiode arrays show long-term biocompatibility, and provide retinal stimulation upon illumination with IR flash. This proposal represents the final two stages of system development in rat and cat models of RP, prior to clinical trials. The proposed experiments will assess: stimulation efficacy and safety limits, long term biocompatibility, and limits of spatial resolution with flat and 3-dimensional implants in electrophysiological and behavioral experiments. PUBLIC HEALTH RELEVANCE: The two leading causes of untreatable blindness in the developed world are retinitis pigmentosa (RP) and end-stage age-related macular degeneration (AMD). Both diseases result in the loss of photoreceptors, while most of the signal processing neurons in the retina are preserved. We propose to restore sight of the blind by delivering visual information to the remaining cells in the neural retina using high resolution electrical stimulation by a photovoltaic subretinal prosthesis. This optoelectronic system represents an innovative and versatile design that addresses the divergent needs of patients with both RP and AMD.