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 视网膜退化性和营养不良的病理是通过 寿命。因此，迫切需要找到可以解决这个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启动刺激剂 （GNES）就是这样一种设备，一种没有外部发电的植入物来刺激 剩余的视网膜神经节细胞以恢复视力。金纳米颗粒放在介电层上 具有在暴露于某些波长时产生电压的效力。有趣的是，这些 可以利用现象将其用作光感受器。长期目标是解决 需要生物相容性的神经感觉设备，修改了高分辨率和 视网膜营养不良和退化患者的持久GNE。拟议的研究 将评估可以被动地混合光学信号效果的自主GNE和 直接激发剩余的视网膜神经节细胞。这项研究的理由是黄金 纳米颗粒是产生颗粒的电压，无需图像处理，功率 眼内和眼外成分的源或广泛的手术。目的 应用是将GNES修饰为视网膜神经节细胞刺激剂。总体假设是 介电平台上的金纳米颗粒可以用作独立的神经刺激器 激发RGC，具有持久的兴奋能力生物相容性。假设将是 通过两个特定目的测试：1。使用GNES设备评估RGC的激发。 GNES激发将使用两种方法进行评估。首先使用多电极阵列（MEA）与 人类干细胞诱导GNE的RGC生长。此外，我们将在基因上使用 编码的钙指示剂（GECI）小鼠与缺乏感光体的RD1小鼠交叉。我们 将测试GNES对不同波长和空间分辨率的响应。 2。确定 带有轻便快门阀（LSV）的精制GNE的可行性。电气中的关注点之一 刺激使系统过热或恒定刺激的神经毒性作用。效果 RGC生存的LSV将通过长时间的视网膜外植体测试。形态和 长期培养或暴露于刺激后，将测试RGC的功能测定。这 工作是创新的，因为它是第一个具有独立能力和 调节光的能力。这项工作非常重要，因为它将定义GNE和 LSV是解决临床挑战的新工具，以治疗感光者丧失的患者， 导致发展新方法来恢复视力。