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; 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.

项目摘要/摘要 至关重要的是将常规神经节细胞（RGC）疗法从实验室转换为诊所，尤其是细胞 移植疗法修复退化的眼组织并恢复视觉功能。 RGC移植很棒 治疗退化性视网膜和视神经疾病的潜力，但关键的临床前研究受到了阻碍 无法跟踪移植细胞。在这个项目中，候选人提出了推进RGC移植的建议 通过基于纳米颗粒的纵向和非侵入性跟踪治疗青光眼 光学相干断层扫描（OCT）对比剂。这些纳米颗粒将被定制为标签和 可视化具有高空间分辨率的RGC。 RGC在体内的纵向跟踪可以揭示命运 捐赠者RGC，增加我们对眼睛行为的理解，并确定影响的因素 RGC移植的治疗效率。在此应用中，PI首先提出使用光谱OCT信号 金纳米棒（GNR）的含量最大化了OCT成像中供体RGC和视网膜之间的对比度。第二， PI的提议要检查GNR的OCT信号与供体RGC的命运之间的相关性 体外和体内测定。第三，PI的提议测试细胞数和注入位置的影响 移植成功率，并利用先进的成像来优化RGC移植。全面的， 基于GNR的OCT对比剂的调查，用于体内RGC跟踪将获得我们的基本知识 RGC移植和前进RGC移植对青光眼治疗的效率。这些数据将有助于 达到PI的整体职业目标，调查可以跟踪，支持和控制治疗细胞的生物材料 体内并使用这些生物材料提供新的方法来治疗原本无法治愈的疾病。在 该奖项的指导阶段，候选人将优先考虑从事的活动，以增加理解和 在斯坦福大学的眼科部门的OCT和青光眼领域接受动手训练 世界一流的分子成像计划和杰出材料科学与工程的支持 斯坦福大学的社区，并带有密切联系和重点部门的好处 更全面的大学的跨学科合作和资源。