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.

项目总结/摘要 视网膜变性会导致失明，因为失去了光感受器。然而，一个重大的 大量的内层视网膜神经元在很大程度上存活下来，这为神经元的生长提供了机会。 通过电刺激这些细胞恢复视力。我们开发了一种光伏 光感受器的替代品，它直接将光转换为脉冲电流， 像素，刺激附近的二级神经元。在萎缩性肌萎缩性侧索硬化盲态患者中进行的临床试验 视网膜相关黄斑变性证实了这种植入物的安全性、稳定性和空间 分辨率与100µm像素尺寸非常匹配。然而，目前的几何单位 双极像素不允许像素尺寸的显著减小， 刺激阈值更小的像素。 我们将制定三个互补的方法来应对这一挑战， 可将像素尺寸减小至20µm，从而实现高度功能恢复 的视线。代替在双极设计的每个像素中使用局部返回电极，我们将使用 单极像素，其有源电极可以用作阳极和阴极。在这 设计，返回电流通过使用集成分流电阻的暗像素流动， 电场更深地穿透到视网膜中。此外，我们将使用光学控制 用于增强场约束的电流导引。它可以调整横向和轴向 通过光伏时空光学调制限制组织中的电场 阵我们还将使用柱状电极：利用视网膜内神经元迁移到视网膜内。 视网膜下植入物中的空隙，支柱顶部的刺激电极更接近 目标细胞。这样，刺激阈值降低，并且双极的选择性降低。 细胞刺激增加。所有这三种方法都可以结合起来，每一种都已经 已经取得了非常令人鼓舞的初步成果，现在将充分发挥这些成果 最终过渡到临床试验的程度。