Gold nanoparticle Neurosensory Epiretinal Implant to Treat Photoreceptor Vision Loss

金纳米颗粒神经感觉视网膜前植入物治疗感光器视力丧失

• 批准号: 10528012
• 负责人: Amir Reza Hajrasouliha
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10528012
• 关键词: Address; Age related macular degeneration; Biological Assay; Blindness; Calcium Channel; Cell Survival; Clinical; Data; Development; Devices; Disease; Electric Stimulation; Electrodes; Exposure to; Eye; Eye diseases; FDA approved; Frequencies; Generations; Goals; Gold; Human; Image; Implant; Light; Light Cell; Lighting; Location; Longevity; Measurement; Measures; Methods; Mission; Modeling; Morphology; Mus; Nanotechnology; National Eye Institute; Neurons; Operative Surgical Procedures; Optics; Pathology; Patients; Perception; Photoreceptors; Power Sources; Procedures; Property; Prosthesis; Public Health; Research; Research Support; Resolution; Retina; Retinal Degeneration; Retinal Dystrophy; Retinal Ganglion Cells; Retinitis Pigmentosa; Signal Transduction; Stimulus; Structure; System; Testing; Tissues; Transgenic Mice; Ultraviolet Rays; Visible Radiation; Vision; Visual impairment; Work; base; biomaterial compatibility; calcium indicator; cell growth; design; dielectric property; experimental study; human stem cells; image processing; implantable device; improved; innovation; light effects; mouse model; multi-electrode arrays; nanoGold; nanoparticle; nanowire; neurosensory; neurotoxic; novel; novel therapeutics; operation; particle; patient population; response; restoration; retinal prosthesis; retinal stimulation; sight restoration; therapy development; titanium dioxide; tool; two photon microscopy; voltage

PROJECT ABSTRACT The retinal degenerative and dystrophic pathologies are major causes of blindness through the lifespan. There is thus a critical need to find novel therapeutic devices which can address this broad group of devastating diseases. Gold-nanoparticle neurosensory epiretinal stimulator (GNES) is one such device, an implant without external power generation for stimulation of remaining retinal ganglion cells to restore vision. Gold nanoparticles placed on a dielectric layer have the potency to generate voltage on exposure to certain wavelengths. Intriguingly, these phenomena can be exploited to use them as photoreceptors. The long-term goal is to address the need for biocompatible neurosensory devices, modifying the design for high resolution and long lasting GNES for patients with retinal dystrophy and degenerations. The proposed research will assess an autonomous GNES that can passively mix the effect of optical signals and directly excite remaining retinal ganglion cells. The rationale for this research is that gold- nanoparticles are voltage generating particles without the need for image processing, power source or extensive surgery for the intraocular and extraocular component. The objective in this application is to modify GNES as a retinal ganglion cell stimulator. The overall hypothesis is that gold nanoparticles on a dielectric platform can serve as a stand-alone neurostimulator that excites RGCs and are biocompatible with lasting excitatory capability. The hypothesis will be tested via two specific aims: 1. Assess the excitation of RGCs ex vivo using GNES device. GNES excitation will be assessed using two methods. First with multielectrode array (MEA) with human stem cell induced RGCs growth over GNES. In addition, we will use Genetically Encoded Calcium Indicator (GECI) mice crossed with rd1 mice which lack photoreceptors. We will test the GNES response to different wavelengths and spatial resolution. 2. Determine the feasibility of refined GNES with Light Shutter Valve (LSV). One of the concerns in electrical stimulation is overheating the system or neurotoxic effect of constant stimulation. The effect of LSV on RGC survival will be tested with prolonged retinal explants. The morphology and functional assay of RGCs will be tested after prolonged culture or exposure to stimulation. This work is innovative, as it is the first epiretinal implantable device with standalone capability and capacity to regulate the light. The work is highly significant because it will define GNES and LSV as a new tool to address the clinical challenge in treating patients with photoreceptor loss, leading to development of new ways to restore vision.

项目摘要 视网膜变性和营养不良病理是导致失明的主要原因 寿命。因此，迫切需要找到能够解决这一问题的新型治疗设备 广泛的毁灭性疾病。金纳米颗粒神经感觉视网膜前刺激器 （GNES）就是这样一种设备，一种无需外部发电即可刺激的植入物 剩余的视网膜神经节细胞恢复视力。放置在介电层上的金纳米颗粒 暴露于某些波长时具有产生电压的能力。有趣的是，这些 可以利用这些现象将它们用作光感受器。长期目标是解决 对生物相容性神经感觉设备的需求，修改设计以获得高分辨率和 针对视网膜营养不良和变性患者的长期 GNES。拟议的研究 将评估一个自主 GNES，它可以被动地混合光信号的影响和 直接兴奋剩余的视网膜神经节细胞。这项研究的基本原理是，黄金 纳米粒子是产生电压的粒子，无需图像处理、电源 来源或广泛的眼内和眼外成分手术。本次活动的目的是 应用是将GNES修改为视网膜神经节细胞刺激器。总体假设是 介电平台上的金纳米粒子可以作为独立的神经刺激器 兴奋 RGC 并具有生物相容性和持久的兴奋能力。假设将是 通过两个具体目标进行测试： 1. 使用 GNES 装置评估离体 RGC 的兴奋情况。 GNES 激励将使用两种方法进行评估。首先采用多电极阵列 (MEA) 人类干细胞诱导 RGC 在 GNES 上生长。此外，我们将使用基因 编码钙指示剂 (GECI) 小鼠与缺乏光感受器的 rd1 小鼠杂交。我们 将测试 GNES 对不同波长和空间分辨率的响应。 2. 确定 使用光快门阀 (LSV) 改进 GNES 的可行性。电气方面关注的问题之一 刺激是使系统过热或持续刺激的神经毒性作用。的效果 LSV 对 RGC 存活的影响将通过延长的视网膜外植体进行测试。形态和 RGC 的功能测定将在长时间培养或暴露于刺激后进行测试。这 这项工作具有创新性，因为它是第一个具有独立功能的视网膜前植入设备， 调节光的能力。这项工作非常重要，因为它将定义 GNES 和 LSV 作为一种新工具来解决治疗光感受器丧失患者的临床挑战， 导致恢复视力的新方法的开发。