Electronic photoreceptors for restoration of sight in retinal degeneration

电子感光器用于视网膜退化患者恢复视力

• 批准号: 10708374
• 负责人: DANIEL V PALANKER
• 金额: $ 68.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708374
• 关键词: 3-Dimensional; Address; Adoption; Algorithms; Anatomy; Anodes; Blinded; Blindness; Cathodes; Cells; Clinical; Clinical Trials; Computer Models; Contrast Sensitivity; Darkness; Electric Stimulation; Electrodes; Electrolytes; Electronics; Geometry; Image; Implant; Lateral; Letters; Light; Lighting; Maps; Measures; Mediating; Neurons; Nonexudative age-related macular degeneration; Ocular Prosthesis; Optics; Patients; Pattern; Penetration; Peripheral; Photoreceptors; Physiologic pulse; Prosthesis; Rattus; Resolution; Retina; Retinal Degeneration; Safety; Sampling; Shapes; Shunt Device; Technology; Tissues; Vision; Visual Acuity; design; electric field; field study; functional restoration; ganglion cell; geographic atrophy; in vivo; migration; neuronal survival; research clinical testing; retinal neuron; retinal stimulation; sight restoration; spatiotemporal; visual information

Project Summary/Abstract Retinal degeneration leads to blindness due to loss of photoreceptors. However, a significant number of the inner retinal neurons survive to a large extent, providing an opportunity for a restoration of vision by electrical stimulation of these cells. We developed a photovoltaic substitute of the photoreceptors, which directly converts light into pulsed electric current in each pixel, stimulating the nearby second-order neurons. Clinical trial in patients blinded by atrophic Age-related Macular Degeneration confirmed the safety, stability of such implants and spatial resolution closely matching the 100µm pixel size. However, the current geometry of the flat bipolar pixels does not allow significant decrease of the pixel size due to rapid increase of the stimulation threshold with smaller pixels. We will develop three complimentary approaches to this challenge, which should enable decreasing the pixel size down to 20µm and thereby enable highly functional restoration of sight. Instead of using local return electrodes in each pixel of a bipolar design, we will use monopolar pixels whose active electrodes can serve as both, anodes and cathodes. In this design, the return current flows via dark pixels using integrated shunt resistors, which enables deeper penetration of electric field into the retina. In addition, we will use optically-controlled current steering for enhanced field confinement. It enables adjustment of the lateral and axial confinement of electric field in tissue by spatiotemporal optical modulation of the photovoltaic array. We will also use pillar electrodes: utilizing the migration of the inner retinal neurons into the voids in the subretinal implant, the stimulating electrode on top of a pillar gets closer to the target cells. This way, the stimulation threshold is decreased and selectivity of the bipolar cells stimulation increased. All three approaches can be combined, each already demonstrated very encouraging preliminary results, and now they will be developed to the full extent for eventual transition into clinical testing.

项目概要/摘要 视网膜变性会因感光细胞丧失而导致失明。然而，一个重要的 视网膜内神经元的数量在很大程度上存活下来，为 通过电刺激这些细胞来恢复视力。我们开发了光伏 替代光感受器，直接将光转换成每个光感受器的脉冲电流 像素，刺激附近的二阶神经元。萎缩性失明患者的临床试验 年龄相关性黄斑变性证实了此类植入物的安全性、稳定性和空间性 分辨率与 100μm 像素尺寸非常匹配。然而，当前公寓的几何形状 双极像素不允许由于像素尺寸的快速增加而显着减小像素尺寸 具有较小像素的刺激阈值。 我们将开发三种互补的方法来应对这一挑战，这应该 能够将像素尺寸减小至 20μm，从而实现高性能修复 的视线。我们不会在双极设计的每个像素中使用局部返回电极，而是使用 单极像素，其有源电极可以同时充当阳极和阴极。在这个 设计中，返回电流使用集成分流电阻器流过暗像素，这使得 电场更深地渗透到视网膜。此外，我们将使用光控 用于增强场限制的电流控制。它可以调节横向和轴向 通过光伏的时空光调制来限制组织中的电场 大批。我们还将使用柱电极：利用内部视网膜神经元迁移到 视网膜下植入物中的空隙，柱顶部的刺激电极变得更接近 靶细胞。这样，刺激阈值降低，双极的选择性 细胞刺激增加。所有三种方法都可以结合起来，每种方法都已经 展示了非常令人鼓舞的初步成果，现在它们将得到充分发展 最终过渡到临床测试的程度。