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 视网膜退化性疾病导致失明，由于失去感光因子而导致失明，而神经元中的神经元 内部残留层在很大程度上保存。电子视网膜假体试图重新引入 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。 第一个残留物的临床结果表明，假肢视力对患者盲目的可行性 通过视网膜变性。但是，当前的假体提供了非常低的分辨率，并得到了动力 通过电感线圈，需要非常复杂的手术方法来植入连接到的电源 通过反式电缆刺激视网膜刺激阵列。 我们开发了一个光伏下的下假体，其中每个像素中的硅光二极管直接 将从视频护目镜投射的脉冲近红外图像转换为本地电流，以刺激 附近的神经元。该系统比其他设计具有多个优点：（1）无线系统可扩展 到植入物中成千上万的像素； （2）模块化设计极大地简化了手术，允许瓷砖匹配 眼曲并扩大视野； （3）刺激模式在视网膜上的投影保持 眼动和图像感知之间的自然联系； （4）网络介导的模拟保留 残留信号处理的几个重要特征，包括闪烁融合，适应静态 在接受场中亚基的图像和非线性求和，这可以实现高空间分辨率。 我们证明，像素大小降低到70 µm，在残留的啮齿动物模型中的假肢视力 退化与像素螺距相匹配，对应于人眼中约20/250的敏锐度。植入 在视网膜下空间中耐受良好 一个月随访）。当该系统过渡到临床试验时，我们建议将 分辨率，研究慢性刺激下的残余变化，并探索细胞内连通性。在 特别是，我们将开发具有更高像素密度的光伏阵列。提高接近度并增加 电极表面积，我们将将支柱电极与光伏像素集成。我们将探索 退化过程中残留接线的变化以及慢性刺激对残余可塑性的影响。在 此外，我们还将探索纳米电极的细胞连接整合的可行性。如果成功，他们 可能会大大降低模拟阈值 - 直至环境光级别，更多 自然引入视觉信息，包括模仿ON和ON的兴奋和抑制投入 关闭剩余途径。

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