Electronic photoreceptors for restoration of sight in retinal degeneration

项目摘要/摘要 视网膜变性由于光感受器的丧失而导致失明。然而，一个重要的 视网膜内神经元的数量在很大程度上存活下来，为 通过电刺激这些细胞来恢复视力。我们开发了一种光伏 光感受器的替代品，它直接将光转化为脉冲电流 象素，刺激附近的二阶神经元。萎缩性失明患者的临床试验 老年性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100微米像素大小非常匹配。然而，目前公寓的几何形状 双极像素不允许显著减小像素大小，因为 像素较小的刺激阈值。 我们将制定三种相辅相成的方法来应对这一挑战， 支持将像素大小降低到20µm，从而实现高功能恢复 视线范围内。我们将在双极设计的每个像素中使用局部返回电极，而不是使用 单极像素，其有源电极既可用作阳极，又可用作阴极。在这 设计中，回流电流通过使用集成并联电阻的暗像素流动，从而实现 电场更深入地渗透到视网膜。此外，我们将使用光控 用于增强场限制力的电流转向。它可以调整横向和轴向 光伏时空光调制对组织中电场的限制 数组。我们还将使用柱状电极：利用视网膜内部神经元的迁移进入 视网膜下植入物中的空洞，柱子顶部的刺激电极更接近 目标单元格。这样，刺激阈值降低了，并且双极的选择性 细胞刺激作用增强。所有这三种方法都可以组合在一起，每种方法都已经 展示了非常令人鼓舞的初步结果，现在它们将得到充分发展 最终过渡到临床测试的程度。

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.