Nanoparticle-Based Tracking of Retinal Ganglion Cell Transplant

基于纳米颗粒的视网膜神经节细胞移植追踪

• 批准号: 10663516
• 负责人: Fang Chen
• 金额: $ 15.18万
• 依托单位: STANFORD UNIVERSITY
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663516
• 关键词: Address; Affect; Age related macular degeneration; Animals; Apoptotic; Area; Award; Behavior; Biocompatible Materials; Biological Assay; Biomedical Engineering; Blindness; Cell Count; Cell Therapy; Cell Transplantation; Cells; Charge; Clinic; Communities; Contrast Media; Cornea; Data; Disease; Disease model; Engineering; Eye; Eye diseases; Face; Faculty; Gel; Glaucoma; Goals; Gold; Image; Immunohistochemistry; In Vitro; Inductively Coupled Plasma Mass Spectrometry; Injections; Injury; Investigation; Knowledge; Label; Laboratories; Lasers; Location; Mentors; Methods; Microglia; Modeling; Molecular; Mus; Natural regeneration; Neonatal; Nerve Crush; Neurodegenerative Disorders; Oils; Ophthalmology; Ophthalmoscopy; Optic Nerve; Optical Coherence Tomography; Outcome; Patients; Peripheral; Phase; Prevalence; Process; Prognosis; Reaction; Research; Research Personnel; Resolution; Resources; Retina; Retinal Degeneration; Retinal Ganglion Cells; Rodent; Scanning; Signal Transduction; Silanes; Silicon; Silicon Dioxide; Site; Structure of retinal pigment epithelium; Surface; Testing; Therapeutic; Thick; Thinness; Time; Tissues; Training; Translating; Transplantation; Treatment Efficacy; Universities; Vision; Visualization; beta Actin; career; clinical application; design; diagnostic strategy; experimental study; imaging program; improved; in vivo; interdisciplinary collaboration; materials science; molecular imaging; nanoGold; nanoparticle; nanorod; novel; novel diagnostics; optic nerve disorder; pre-clinical; preclinical study; repaired; retinal damage; retinal imaging; sight restoration; skills; success; tool; transplantation therapy; uptake

Project Summary/Abstract There is a critical need to translate retinal ganglion cell (RGC) therapies from lab to clinic, particularly cell transplant therapies to repair degenerated eye tissues and restore visual function. RGC transplant has great potential in treating degenerative retinal and optic nerve diseases, but key pre-clinical studies are hampered by an inability to track transplanted cells. In this project, the candidate proposes to advance RGC transplant in treating glaucoma through longitudinal and non-invasive tracking of RGCs with the aid of nanoparticle-based optical coherence tomography (OCT) contrast agents. These nanoparticles are to be customized to label and visualize RGCs with a high spatial resolution. Longitudinal tracking of the RGCs in vivo could uncover the fate of the donor RGCs, increase our understanding of their behavior in the eye, and identify the factors that affect the treatment efficacy of RGC transplants. In this application, the PI first proposes to use spectral OCT signals of gold nanorods (GNRs) to maximize the contrast between donor RGCs and the retina in OCT imaging. Second, the PI proposes to examine the correlation between the OCT signals of GNRs and the fate of donor RGCs with both in vitro and in vivo assays. Third, the PI proposes to test the effects of cell number and injection location on the transplant success rate, and to leverage advanced imaging to optimize RGC transplantation. Overall, investigations in GNR-based OCT contrast agents for in vivo RGC tracking will gain us essential knowledge in the efficacy of RGC transplant and advance RGC transplant for glaucoma treatment. These data will contribute to the PI’s overall career goals, to investigate biomaterials that could track, support, and control therapeutic cells in vivo and to use these biomaterials to provide novel methods to treat otherwise incurable diseases. During the mentored phase of this award, the candidate will prioritize undertaking activities to increase understanding and gain hands-on training in the areas of OCT and glaucoma in the Department of Ophthalmology at Stanford, with support from the world-class Molecular Imaging Program and the outstanding Materials Science & Engineering Community at Stanford, and with the benefits of a close-knit and focused department and the multi- interdisciplinary collaborations and resources of the more comprehensive university.

项目总结/摘要 迫切需要将视网膜神经节细胞（RGC）疗法从实验室转化为临床，特别是细胞治疗。 移植治疗，以修复退化的眼组织和恢复视觉功能。RGC移植有很大的 潜在的治疗退行性视网膜和视神经疾病，但关键的临床前研究受到阻碍， 无法追踪移植的细胞在这个项目中，候选人建议在 借助于基于纳米颗粒的药物通过纵向和非侵入性追踪RGCs治疗青光眼 光学相干断层扫描（OCT）造影剂。这些纳米颗粒将被定制以标记和 以高空间分辨率可视化RGC。体内RGCs的纵向追踪可以揭示 的供体RGC，增加我们对他们的行为在眼睛的理解，并确定影响的因素， RGC移植的治疗效果。在此应用中，PI首先建议使用光谱OCT信号 金纳米棒（GNRs），以最大限度地提高OCT成像中供体RGC和视网膜之间的对比度。第二、 PI建议检查GNRs的OCT信号与供体RGC命运之间的相关性， 在体外和体内测定中。第三，PI建议测试细胞数量和注射位置对 移植成功率，并利用先进的成像技术来优化RGC移植。总的来说， 对用于体内RGC跟踪的基于GNR的OCT造影剂的研究将使我们获得以下基本知识： RGC移植和高级RGC移植治疗青光眼的疗效。这些数据将有助于 PI的总体职业目标，研究可以跟踪，支持和控制治疗细胞的生物材料 并使用这些生物材料提供治疗其他不可治愈疾病的新方法。期间 在该奖项的指导阶段，候选人将优先考虑开展活动，以提高理解和 在斯坦福大学眼科获得OCT和青光眼领域的实践培训， 来自世界一流的分子成像计划和杰出的材料科学与工程的支持 社区在斯坦福大学，并与一个紧密联系和重点部门的好处和多- 跨学科的合作和资源更全面的大学。