Functional analysis of an LGN-based visual prosthesis

我们正在研制一种能使盲人恢复视力的视觉假体。找到治疗失明的方法 重要的是，预计到2030年，每28名45岁以上的人中就有1人受到影响（约占人口的3.5%）。 其中包括10万多名退伍军人。此外，失明与增加的 抑郁症、肥胖症、糖尿病和意外福尔斯，估计三分之二的盲人是 失业潜在的治疗方法正在开发中，包括药物，遗传，干细胞， 光遗传学和假体方法，但几乎所有的目标是视网膜，因此提供了一个大的希望不大， 部分盲人。这包括战场士兵，从战斗中返回， 眼睛受伤，以及其他患有类似疾病的普通人群。它还包括那些与 青光眼、年龄相关性黄斑变性和糖尿病视网膜病变，这三种最常见的致盲原因 老年退伍军人（和一般人群）。丘脑的外侧膝状体核（LGN）是一个神经元， 假体植入的有吸引力的部位，因为它超出了与大多数原因相关的疾病/创伤 因此，一种有效的装置将为大部分盲人提供治疗。在 此外，LGN比视网膜在空间上更扩张，因此允许更大数量的刺激 网站和更高的敏锐度。同时，LGN神经元使用的神经信号模式要少得多 比视觉皮层更抽象，从而允许更直接的编码方案（比 皮质假体所需的那些）。虽然开发高计数、多通道的 一种可以安全植入大脑深层结构的设备，我们的同事最近开发了这样一种设备， 设备和许多努力正在进行中，以推进这项技术。然而，人们对如何 有效地刺激LGN与假肢，这种缺乏了解将阻碍进展， 临床器械。在这里，我们提出了4个目标，重点是学习如何有效地驱动LGN神经元， 假肢我们的初步测试表明，来自LGN的刺激确实可以驱动下游视觉， 此外，初级视觉皮层（V1）也被激活（继发于LGN的激活）。 因此，我们的目标将集中在确定如何最有效地激活LGN，我们将探讨是否 使LGN激活最大化的相同条件也产生视觉皮层的强激活。的一部分 在这项研究中，我们还将探讨LGN中的单个细胞类型是否对电刺激具有不同的敏感性。 刺激的情况下，在许多其他地区的中枢神经系统。这将是非常有用的，因为不同层的 LGN由不同的细胞类型组成，了解如何最佳地激活每种细胞类型可能会导致更好的 结果。最后，我们将评价长期植入器械的性能稳定性。 我们认为，这里提议的全面评估将提供一个基础， 系统地推进未来临床前和临床研究。

We are developing a visual prosthesis that can restore vision to the blind. Finding a treatment for blindness is significant as it is projected to impact 1 in 28 individuals over the age of 45 by the year 2030 (~3.5% of the population), including over 100,000 Veterans. Further, blindness is associated with increased levels of depression, obesity, diabetes, and accidental falls, and estimates suggest two-thirds of the blind are unemployed. Potential treatments are under development, including pharmaceutical, genetic, stem cell, optogenetic and prosthetic approaches, but almost all target the retina and thus offer little hope to a large portion of the blind population. This includes battlefield soldiers, returning from combat with bilateral traumatic eye injury, and other members of the general population with similar afflictions. It also includes those with glaucoma, age-related macular degeneration, and diabetic retinopathy, the 3 most common cause of blindness in aging Veterans (and the general population). The lateral geniculate nucleus (LGN) of the thalamus is an attractive site for implantation of a prosthesis as it is beyond the disease/trauma associated with most causes of blindness and thus a working device would offer a treatment to large portions of the blind population. In addition, the LGN is more spatially expansive than the retina and thus allows for a larger number of stimulation sites and higher acuity. At the same time, the neural signaling patterns used by LGN neurons are much less abstract than those of the visual cortex, thereby allowing for more straightforward encoding schemes (than those required by cortical prostheses). While it has been challenging to develop a high-count, multi-channel device that can safely be implanted into a deep brain structure, our colleagues have recently developed such a device and much effort is underway to advance this technology. However, little is known about how to effectively stimulate the LGN with a prosthesis and this lack of understanding will impede progress towards a clinical device. Here, we propose 4 Aims focused on learning how to effectively drive LGN neurons with a prosthesis. Our initial testing shows that stimulation from of the LGN can indeed drive downstream visual circuits and further, that primary visual cortex (V1) is activated as well (secondary to the activation of the LGN). Thus, our Aims will focus on determining how to most effectively activate the LGN and we will explore whether the same conditions that maximize LGN activation also produce robust activation of visual cortex. As part of this investigation, we will also explore whether individual cell types in LGN have different sensitivities to electric stimulation as is the case in many other regions of the CNS. This will be quite useful as the different layers of LGN are comprised of different cell types and understanding how to optimally activate each may lead to better outcomes. Finally, we will evaluate the stability of performance for implanted devices for chronic implantation. We believe that the comprehensive evaluation proposed here will provide a foundation from which to systematically advance future pre-clinical and clinical studies.