Photovoltaic Subretinal Prosthesis with High Pixel Density

高像素密度光伏视网膜下假体

• 批准号: 9897371
• 负责人: DANIEL V PALANKER
• 金额: $ 18.96万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897371
• 关键词: 3-Dimensional; Age related macular degeneration; Animals; Apoptosis; Area; Blinded; Blindness; Blood Vessels; Cell Culture Techniques; Cells; Characteristics; Chronic; Clinical; Clinical Trials; Complex; Contrast Sensitivity; Electric Stimulation; Electrodes; Electroplating; Endocytosis; Evoked Potentials; Eye; Eye Movements; Flicker Fusion; Frequencies; Goggles; Height; Human; Image; Implant; Inner Nuclear Layer; Lead; Light; Lighting; Link; Measurement; Measures; Mediating; Methods; Modeling; Neurons; Ocular Prosthesis; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Perception; Photoreceptors; Physiologic pulse; Power Sources; Process; Property; Prosthesis; Rattus; Resolution; Retina; Retinal; Retinal Degeneration; Retinitis Pigmentosa; Rodent; Rodent Model; Safety; Severities; Shapes; Silicon; Structure; Surface; Synapses; System; Time; Vision; Visual Acuity; Visual Fields; Visual system structure; Wireless Technology; awake; base; cell motility; density; design; follow-up; high resolution imaging; improved; in vivo; multi-electrode arrays; nanoelectrodes; neural stimulation; new technology; preservation; receptive field; relating to nervous system; response; restoration; retina implantation; retinal prosthesis; signal processing; visual information

Project Summary/Abstract Retinal degenerative diseases lead to blindness due to loss of photoreceptors, while neurons in the inner retinal layers are preserved to a large extent. Electronic retinal prostheses seek to reintroduce information into the visual system and thereby restore sight by electrical stimulation of surviving neurons. Clinical results with the first retinal implants demonstrated feasibility of prosthetic vision in patients blinded by retinal degeneration. However, current prostheses provide very low resolution, and being powered through inductive coils, require very complex surgical methods to implant the power supply connected to retinal stimulating array via trans-scleral cable. We developed a photovoltaic subretinal prosthesis, in which silicon photodiodes in each pixel directly convert pulsed near-infrared images projected from video goggles into local electric currents to stimulate the nearby neurons. This system offers multiple advantages over other designs: (1) Wireless system is scalable to thousands of pixels in the implant; (2) Modular design greatly simplifies surgery, allows tiling to match the eye curvature and to expand visual field; (3) Projection of stimulating patterns onto the retina maintains natural link between eye movements and image perception; (4) Network-mediated stimulation retains several important features of the retinal signal processing, including flicker fusion, adaptation to static images and non-linear summation of subunits in receptive fields, which enables high spatial resolution. We demonstrated that with pixel sizes down to 70 µm, prosthetic visual acuity in rodent models of retinal degeneration matches the pixel pitch, corresponding to about 20/250 acuity in the human eye. The implants are well tolerated in the subretinal space, and responses are stable during the lifetime of the animals (12- month follow-up). While this system is being transitioning into clinical trials, we propose to double the resolution, study retinal changes under chronic stimulation, and explore intracellular connectivity. In particular, we will develop photovoltaic arrays with higher pixel density. To improve proximity and increase electrode surface area, we will integrate pillar electrodes with photovoltaic pixels. We will explore the changes in retinal wiring during the degeneration, and the effect of chronic stimulation on retinal plasticity. In addition, we will explore feasibility of the cell-attached integration of nanoelectrodes. If successful, they might enable greatly reduced stimulation thresholds – down to the ambient light levels, and much more natural introduction of the visual information, including excitatory and inhibitory inputs mimicking the ON and OFF retinal pathways.

项目概要/摘要 视网膜退行性疾病由于光感受器的丧失而导致失明，而视网膜中的神经元 电子视网膜假体试图在很大程度上保留视网膜内层。 信息进入视觉系统，从而通过对幸存神经元的电刺激来恢复视力。 第一个视网膜植入物的临床结果证明了失明患者假体视力的可行性 然而，目前的假体分辨率非常低，并且需要供电。 通过感应线圈，需要非常复杂的手术方法来植入连接的电源 通过经巩膜电缆的视网膜刺激阵列。 我们开发了一种光伏视网膜下假体，其中每个像素中的硅光电二极管直接 将视频护目镜投射的脉冲近红外图像转换为局部电流以刺激 与其他设计相比，该系统具有多种优势：(1) 无线系统具有可扩展性。 植入物中有数千个像素；(2) 模块化设计大大简化了手术，允许平铺匹配 (3) 刺激图案投射到视网膜上保持 眼球运动和图像感知之间的自然联系；（4）网络介导的刺激保留 视网膜信号处理的几个重要特征，包括闪烁融合、静态适应 图像和感受野中子单元的非线性求和，从而实现高空间分辨率。 我们证明，当像素尺寸小至 70 µm 时，啮齿动物视网膜模型中的假体视力 退化与像素间距相匹配，相当于人眼的约 20/250 敏锐度。 在视网膜下腔中具有良好的耐受性，并且在动物的一生中反应是稳定的（12- 当该系统正在过渡到临床试验时，我们建议将其加倍。 分辨率，研究慢性刺激下的视网膜变化，并探索细胞内连接。 特别是，我们将开发具有更高像素密度的光伏阵列，以提高接近度并增加。 电极表面积，我们将探索将柱电极与光伏像素集成。 退化过程中视网膜布线的变化，以及慢性刺激对视网膜可塑性的影响。 此外，我们还将探索纳米电极附着于细胞的可行性，如果成功的话。 可能会大大降低刺激阈值——低至环境光水平等等 视觉信息的自然引入，包括模仿 ON 和 ON 的兴奋性和抑制性输入 关闭视网膜通路。