Photovoltaic Subretinal Prosthesis with High Pixel Density

高像素密度光伏视网膜下假体

• 批准号: 10171857
• 负责人: DANIEL V PALANKER
• 金额: $ 59.19万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171857
• 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; Near-infrared optical imaging; Neurons; Ocular Prosthesis; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Perception; Photoreceptors; Physiologic pulse; Power Sources; Process; Property; Prosthesis; Rattus; Resolution; Retina; 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; retina implantation; retinal prosthesis; sight restoration; 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.

项目摘要/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 视网膜内层在很大程度上得到了保护。电子视网膜假体寻求重新引入 信息进入视觉系统，从而通过电刺激存活的神经元恢复视力。 首次植入视网膜的临床结果证明了盲人使用人工视力的可行性。 由视网膜退化引起。然而，目前的假体提供的分辨率非常低，并且是由 通过感应线圈，需要非常复杂的手术方法来植入连接到的电源 经巩膜电缆视网膜刺激阵列。 我们开发了一种光伏视网膜下假体，其中硅光电二极管直接在每个像素上 将视频护目镜投射的脉冲近红外图像转换为当地电流，以刺激 附近的神经元。与其他设计相比，该系统具有多个优点：(1)无线系统可扩展 到数千个像素的种植体；(2)模块化设计大大简化了手术，允许瓷砖与 眼球弯曲和扩大视野；(3)刺激模式在视网膜上的投射保持 眼球运动和图像知觉之间的自然联系；(4)网络介导的刺激保持 视网膜信号处理的几个重要特征，包括闪烁融合、对静态的适应 图像和感受场中子单元的非线性求和，从而实现高空间分辨率。 我们证明了在像素大小降至70微米的情况下，在啮齿类动物的视网膜模型中，人工视力 退化与像素间距匹配，相当于人眼的敏锐度约为20/250。植入物 在视网膜下空间有很好的耐受性，并且在动物的一生中反应稳定(12- 一个月的随访)。虽然这一系统正在过渡到临床试验，但我们建议将 分辨率，研究视网膜在慢性刺激下的变化，并探索细胞内的连接。在……里面 特别是，我们将开发像素密度更高的光伏阵列。改善邻近性并增加 电极表面积，我们将柱电极与光伏像素整合。我们将探索 变性过程中视网膜连线的变化，以及慢性刺激对视网膜可塑性的影响。在……里面 此外，我们还将探索纳米电极细胞附着式集成的可行性。如果成功，他们将 可能会大大降低刺激阈值--低至环境光线水平，等等 视觉信息的自然引入，包括模拟ON和ON的兴奋性和抑制性输入 脱离视网膜通路。

项目成果

Cortical Interactions between Prosthetic and Natural Vision.

• DOI: 10.1016/j.cub.2019.11.028
• 发表时间: 2020-01-06
• 期刊: Current biology : CB
• 作者: Arens-Arad T;Farah N;Lender R;Moshkovitz A;Flores T;Palanker D;Mandel Y
• 通讯作者: Mandel Y

Temporal structure in spiking patterns of ganglion cells defines perceptual thresholds in rodents with subretinal prosthesis.

• DOI: 10.1038/s41598-018-21447-1
• 发表时间: 2018-02-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ho E;Lorach H;Goetz G;Laszlo F;Lei X;Kamins T;Mariani JC;Sher A;Palanker D
• 通讯作者: Palanker D

STEM CELL THERAPIES, GENE-BASED THERAPIES, OPTOGENETICS, AND RETINAL PROSTHETICS: Current State and Implications for the Future.

干细胞疗法、基于基因的疗法、光遗传学和视网膜修复术：现状​​和对未来的影响。

• DOI: 10.1097/iae.0000000000002449
• 发表时间: 2019
• 期刊: Retina (Philadelphia, Pa.)
• 作者: Wood,EdwardH;Tang,PeterH;DelaHuerta,Irina;Korot,Edward;Muscat,Stephanie;Palanker,DanielA;Williams,GeorgeA
• 通讯作者: Williams,GeorgeA

Restoring Sight with Retinal Prostheses.

用视网膜假体恢复视力。

• DOI: 10.1063/pt.3.3970
• 发表时间: 2018
• 期刊: Physics today
• 影响因子: 3.5
• 作者: Palanker,Daniel;Goetz,Georges
• 通讯作者: Goetz,Georges