Gold nanoparticle Neurosensory Epiretinal Implant to Treat Photoreceptor Vision Loss

项目摘要 视网膜退行性和营养不良性病理是失明的主要原因， 寿命因此，迫切需要找到能够解决这一问题的新型治疗装置 广泛的毁灭性疾病。纳米金视网膜神经刺激器 （GNES）是一种这样的装置，一种不需要外部发电来刺激神经系统的植入物。 保留视网膜神经节细胞以恢复视力。置于介电层上的金纳米颗粒 具有在暴露于特定波长时产生电压的潜力。有趣的是，这些 可以利用这种现象将它们用作光感受器。长期目标是解决 需要生物相容的神经感觉装置，修改设计以获得高分辨率， 长效GNES用于视网膜营养不良和变性患者。拟议研究 将评估一个自主的GNES，它可以被动地混合光信号的效果， 直接刺激剩余的视网膜神经节细胞。这项研究的基本原理是，黄金- 纳米颗粒是产生电压的颗粒，而不需要图像处理、功率 眼内和眼外部分的源或广泛手术。在这方面的目标 本申请的目的是将GNES修饰为视网膜神经节细胞刺激剂。总的假设是 介电平台上的金纳米颗粒可以作为一个独立的神经刺激器， 兴奋RGC，并且具有持久兴奋能力的生物相容性。假设是 通过两个具体目标进行测试：1.使用GNES装置评估离体RGC的激发。 将使用两种方法评估GNES激发。首先是多电极阵列（MEA）， 人干细胞诱导RGCs在GNES上生长。此外，我们还将利用基因 编码钙指示剂（GECI）小鼠与缺乏光感受器的rd 1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 改进的GNES与光闸阀（LSV）的可行性。电气领域的一个问题是， 刺激是系统过热或持续刺激的神经毒性作用。的影响 LSV对RGC存活率的影响将通过延长的视网膜外植体进行测试。形态和 将在长时间培养或暴露于刺激后测试RGC的功能测定。这 这项工作是创新的，因为它是第一个具有独立能力的视网膜前植入式设备， 调节光线的能力。这项工作非常重要，因为它将界定全球环境战略， LSV作为一种新的工具，以解决治疗感光细胞丧失患者的临床挑战， 从而开发出恢复视力的新方法。

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.