Photovoltaic Subretinal Prosthesis with High Pixel Density

项目总结/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以保留。电子视网膜假体寻求重新引入 通过电刺激存活的神经元，将信息输入视觉系统，从而恢复视力。 第一个视网膜植入物的临床结果证明了失明患者修复视力的可行性 视网膜退化然而，目前的假体提供非常低的分辨率，并且被供电， 通过感应线圈，需要非常复杂的手术方法来植入连接到 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 附近的神经元与其他设计相比，该系统具有以下优点：（1）无线系统具有可扩展性 （2）模块化设计大大简化了手术，允许平铺以匹配植入物中的 眼曲率和扩大视野;（3）刺激图案在视网膜上的投影维持 眼动和图像感知之间的自然联系;（4）网络介导的刺激保留了 视网膜信号处理的几个重要特征，包括闪烁融合、静态适应 图像和感受野中亚基的非线性总和，这使得能够实现高空间分辨率。 我们证明，像素尺寸降至70 µ m时，啮齿类动物视网膜病变模型中的假体视力 退化匹配对应于人眼中大约20/250敏锐度的像素间距。植入物 在视网膜下空间中耐受良好，并且在动物的一生中反应稳定（12- 月随访）。虽然该系统正在过渡到临床试验，但我们建议将 分辨率，研究慢性刺激下的视网膜变化，并探索细胞内连接。在 特别是，我们将开发像素密度更高的光伏阵列。为了提高接近度， 电极表面积，我们将集成柱电极与光伏像素。我们将探讨 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 此外，我们也将探讨奈米电极在细胞上整合的可行性。如果成功，他们 可以大大降低刺激阈值-降低到环境光水平，等等 视觉信息的自然引入，包括模仿ON的兴奋和抑制输入， 关闭视网膜通路。

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.