Patterned electrical stimulation of the retina for high-resolution prostheses

描述（由申请人提供）：我研究的长期目标是了解视网膜的视觉信号功能，并利用这些知识来治疗失明。这项工作的主要目标是开发精确的、有图案的视网膜多电极刺激技术，以推进高分辨率视网膜假体装置的发展，以取代因变性而受损的视网膜的功能。具体目标包括：(1)唤醒灵长类视网膜主要高分辨率神经节细胞类型的电活动，以及退化的大鼠视网膜中的几种神经节细胞类型；(2)选择性地刺激单个细胞，以获得传递到大脑的正常视觉信号的基本空间和时间分辨率，同时避免刺激轴突，通过一系列视网膜偏心；(3)唤起神经节细胞群体的空间和时空活动模式，这些细胞可以模拟通常传输到大脑的复杂视觉信号。我们将运用我们独特的技术，在体外同时独立地刺激和记录许多神经节细胞，使用的电极阵列与目前使用的视网膜假体相当，但要小得多，密度也要大得多。我们将利用这项技术开发新的方法来模拟视觉信号的焦点和模式刺激，包括开发针对中央视网膜的新技术。我们还将利用我们在灵长类视网膜和P23H突变大鼠视网膜变性模型方面的经验，最大限度地提高研究结果与治疗失明的相关性。我们的愿景是，这项工作将有助于下一代视网膜假体设备的设计，以支持人类患者的先进视觉功能，如物体识别和运动感应。

DESCRIPTION (provided by applicant): The long-term objectives of my research are to understand the visual signaling function of the retina and to exploit this knowledge for the treatment of blindness. The major goal of the proposed work is to develop techniques for precise, patterned multi-electrode stimulation of the retina, with the purpose of advancing the development of high-resolution retinal prosthetic devices to replace the function of retinas damaged by degeneration. The specific aims involve (1) evoking electrical activity in the major high-resolution ganglion cell types of the primate retina, as well as several ganglion cell types in the degenerating rat retina, (2) selectively stimulating individual cells to achieve the elementary spatial and temporal resolution of normal visual signals transmitted to the brain while avoiding stimulation of axons, over a range of retinal eccentricities, and (3) evoking spatial and spatiotemporal patterns of activity in populations of ganglion cells that can mimic the complex visual signals normally transmitted to the brain. We will apply our unique technology to simultaneously and independently stimulate and record from many ganglion cells in vitro, using an array of electrodes comparable to but much smaller and denser than those used in current retinal prosthetics. We will exploit this technology to develop new methods for focal and patterned stimulation to mimic visual signals, including development of novel technologies to target the central retina. We will also leverage our experience with the primate retina and the P23H mutant rat model of retinal degeneration to maximize the relevance of the findings for treating blindness. Our vision is that the work will aid the design of the next generation of retinal prosthetic devices to support advanced visual functions such as object recognition and motion sensing in human patients. PUBLIC HEALTH RELEVANCE: The goal of the proposed work is to advance the development of high-resolution retinal prosthetic devices to treat blindness, using electrophysiological recording and stimulation of the primate and degenerating retina in vitro. Our approach leverages a specialized multi-electrode recording and stimulation technology designed to resemble future prosthetic devices, with an emphasis on emulating naturalistic visual signals and interfacing with the parallel pathways for high-resolution vision in primates. This unique approach will further the design of the next generation of retinal prostheses -- devices that can support advanced visual functions such as object recognition and motion sensing in human patients.