High Resolution Optoelectronic Retinal Prosthesis

描述(申请人提供)：在发达国家，无法治疗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，但它们都有一个共同的结果，即视网膜的感光细胞--光感受器的退化。恢复视觉功能的一种方法是使用视网膜假体刺激剩余的视网膜电路，该假体将视觉信息编码为电信号。挑战是设计这样一个系统，它与患病的视网膜连接，并提供高分辨率的视觉环境表示。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，以完成专门为实现视觉功能水平而设计的高分辨率视网膜假体系统的开发和评估。在该系统中，经过处理的视觉场景图像由脉冲红外光投射到视网膜下放置的微光电二极管阵列上。阵列中的光伏像素将脉冲光转换为直接刺激视网膜神经元的两相电流脉冲。这种光电视网膜假体系统提供了几个新颖而有利的功能：可以同时和独立地激活植入物中的数百或数千个像素，简化了手术程序，用户可调节图像处理，高分辨率刺激，眼睛运动和图像感知之间的自然联系，便于通过刺激电极近距离接触神经元的三维植入物结构，以及允许扩大刺激野的模块化植入物设计。这种多功能系统可以用来满足RP和AMD患者的不同需求。系统的大部分组件已经开发完成，并进行了部分方面的测试。原型光电二极管阵列表现出长期的生物兼容性，并在红外闪光灯照射下提供视网膜刺激。这项建议代表了在临床试验之前，在大鼠和猫的RP模型中系统发展的最后两个阶段。拟议的实验将评估：电生理和行为学实验中平面和三维植入物的刺激效率和安全限度、长期生物相容性和空间分辨率极限。公共卫生相关性：在发达国家，导致无法治愈的失明的两个主要原因是视网膜色素变性(RP)和终末期老年性黄斑变性(AMD)。这两种疾病都会导致光感受器的丧失，而视网膜中的大多数信号处理神经元都得到了保存。我们建议通过使用光伏视网膜下假体的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和多功能的设计，满足了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.