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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/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，特别是细胞疗法移植疗法对修复退化的眼组织和恢复视功能有很大作用。治疗退行性视网膜和视神经疾病的潜力，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，候选人建议推进 RGC 移植。借助基于纳米粒子的 RGC 的纵向和非侵入性跟踪来治疗青光眼这些纳米粒子将被定制以进行标记和成像。以高空间分辨率可视化 RGC 体内的纵向跟踪可以揭示 RGC 的命运。供体 RGC 的研究，增加我们对其眼睛行为的了解，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 (GNR) 可以最大限度地提高 OCT 成像中供体 RGC 和视网膜之间的对比度。 PI 建议检查 GNR 的 OCT 信号与供体 RGC 的命运之间的相关性第三，PI 建议测试细胞数量和注射位置对的影响。移植成功率，并利用先进的成像技术来优化 RGC 移植。对用于体内 RGC 跟踪的基于 GNR 的 OCT 造影剂的研究将为我们获得以下方面的重要知识： RGC移植的疗效和先进的RGC移植对青光眼治疗的贡献。为了 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利用这些生物材料为治疗其他无法治愈的疾病提供新方法。在该奖项的指导阶段，候选人将优先开展活动以增进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世界一流的分子影像项目和杰出的材料科学与工程的支持斯坦福大学的社区，并受益于紧密、专注的部门和多学科的优势更综合性大学的跨学科合作和资源。