Functional analysis of an LGN-based visual prosthesis

基于 LGN 的视觉假体的功能分析

• 批准号: 10582766
• 负责人: Shelley Fried
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582766
• 关键词: Accidental Falls; Age; Age related macular degeneration; Aging; Anatomy; Animals; Area; Bilateral; Blindness; Brain; Cells; Chronic; Clinical; Clinical Research; Development; Device Designs; Devices; Diabetes Mellitus; Diabetic Retinopathy; Disease; Effectiveness; Electric Stimulation; Electrodes; Evaluation; Eye; Eye Injuries; Foundations; Future; General Population; Genetic; Glaucoma; Implant; In Vitro; Individual; Investigation; Lateral Geniculate Body; Learning; Maps; Mental Depression; Mus; Neurons; Obesity; Ocular Prosthesis; Outcome; Pathway interactions; Patients; Pattern; Performance; Pharmacologic Substance; Physiology; Population; Positioning Attribute; Prosthesis; Retina; Scheme; Secondary to; Shapes; Signal Transduction; Site; Soldier; Structure; Surface; Technology; Testing; Thalamic structure; Time; Tissues; Trauma; Unemployment; Veterans; Vision; Visual; Visual Cortex; area striata; blind; cell type; combat; implantable device; implantation; member; neural; neurotransmission; optogenetics; preclinical study; response; retina implantation; sight restoration; stem cells; transmission process

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.

我们正在开发一种视觉假体，可以帮助盲人恢复视力。寻找治疗失明的方法是 意义重大，因为预计到 2030 年，每 28 名 45 岁以上的人中就会有 1 人受到影响（约占 45 岁以上人口的 3.5%） 人口），其中包括超过 100,000 名退伍军人。此外，失明还与 抑郁症、肥胖症、糖尿病和意外跌倒，估计三分之二的盲人 失业了。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，但几乎所有方法都以视网膜为目标，因此对大范围的治疗几乎没有希望 盲人人口的一部分。这包括战场士兵，从战斗中返回双侧创伤 眼睛受伤，以及其他有类似疾病的普通人群。它还包括那些具有 青光眼、年龄相关性黄斑变性和糖尿病性视网膜病变（第三大失明原因） 老年退伍军人（和普通人群）。丘脑的外侧膝状核 (LGN) 是 假体植入的有吸引力的地点，因为它超出了与大多数原因相关的疾病/创伤的范围 失明，因此工作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广阔，因此可以接受更多的刺激 站点和更高的敏锐度。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、多通道一直具有挑战性 我们的同事最近开发了一种可以安全地植入大脑深层结构的装置 设备，并且正在进行大量努力来推进这项技术。然而，人们对如何 用假肢有效地刺激 LGN，这种缺乏理解将阻碍实现这一目标的进展 临床设备。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 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，我们的目标将集中于确定如何最有效地激活 LGN，并且我们将探索是否 最大化 LGN 激活的相同条件也会产生视觉皮层的强烈激活。作为一部分 在这项研究中，我们还将探讨 LGN 中的各个细胞类型是否对电具有不同的敏感性 中枢神经系统许多其他区域的情况也是如此。这将非常有用，因为不同的层 LGN 由不同的细胞类型组成，了解如何最佳地激活每种细胞可能会带来更好的结果 结果。最后，我们将评估长期植入的植入设备的性能稳定性。 我们相信，这里提出的综合评价将为今后的发展奠定基础。 系统地推进未来的临床前和临床研究。