Novel Cell Free Therapy for Glaucoma

青光眼的新型无细胞疗法

• 批准号: 10076404
• 负责人: STEVEN ROTH
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10076404
• 关键词: Adverse effects; Axon; Biological; Blindness; Caliber; Cell Death; Cell Therapy; Cell Transplantation; Cell physiology; Cells; Clinical; Clinical Research; Data Analyses; Data Collection; Development; Disease; Engineering; Ensure; Exposure to; Funding; Glaucoma; Goals; Inflammatory; Knowledge; Medical; Modification; Operative Surgical Procedures; Patients; Physiologic Intraocular Pressure; Precision therapeutics; Reporting; Research; Research Design; Retina; Retinal Diseases; Retinal Ganglion Cells; Review Literature; Route; Schools; Scientist; Site; Specificity; Students; Testing; Therapeutic Uses; Time; Training; Vision; Visual; Writing; axon growth; base; clinical application; clinical translation; cost efficient; design; dosage; excitotoxicity; experience; experimental study; extracellular vesicles; functional loss; improved; innovation; interest; intravitreal injection; nanoparticle; neuroprotection; novel; novel therapeutics; prevent; stem cells; targeted delivery; undergraduate student

A principal unmet need in glaucoma is that medical or surgical intraocular pressure reduction is the only clinically-approved treatment. But vision cannot be restored because retinal ganglion cell (RGC) loss is irre- versible. Knowledge gaps to improved therapy include how to achieve neuroprotection, i.e., preventing RGCs from dying, or, to use cell-based therapy to re-grow or replace. Administration route, dosage, and adverse effects limit clinical application of neuroprotection and cell transplantation. Studying a new treatment using extracellular vesicles (EVs), biologically-active 50-150 nm diameter nanoparticles derived from stem cells, the proposal fills a gap and urgent need in the development of new treatments to prevent RGC death and vision loss for glaucoma patients. EVs represent a potential clinically applicable means to prevent RGC, axonal, and visual functional loss and decreasing the excitotoxic and inflammatory component of glaucoma. Our central hypothesis is that EVs can be designed and optimized to specifically target RGCs as a basis for precision treatment of glaucoma and, ultimately, other retinal diseases. We propose to test engineered EVs as a novel cell-free means to specifically target neuroprotection to RGCs and to fill the knowledge gaps that presently prevent clinical translation of EVs for retinal disease. Our specific aims are Aim 1: Determine the time course and factors regulating the distribution of EVs in the vitreous and retina, and optimize EV delivery to retina. Aim 2: Develop and optimize novel engineered EVs to specifically target RGCs. Successful com- pletion of Aim 1 will optimize delivery of EVs to the retina following intravitreal injection. Aim 2 will guide administration of EVs to produce innovative, specific, targeted delivery into RGCs, allowing specificity for treatment at the major pathophysiological site of glaucoma. Fulfillment of these objectives will set the stage to develop glaucoma therapeutics using EVs by optimizing administration, and by specific RGC-targeted EVs. The study offers promise to save sight via development of safe, effective, and cost-efficient therapy to restore or prevent loss of sight in patients with glaucoma. This contribution is expected to be significant because these studies will provide a basis to develop EVs as a therapy for glaucoma, either primarily restoring RGC function and axonal growth, or optimizing existing therapies such as RGC transplants. Innovative features are cell- free therapy of glaucoma, novel targeted EVs for specific RGC action, and novel delivery materials for EVs. The supplement for Diversity proposes to train an undergraduate student in data collection and analysis, reviewing literature critically, designing experiments, and writing research reports. The student will be involved with the project in the summer and during the school year. The goal is to use this experience to increase the interest of the student in clinical research and ultimately to assist in ensuring more opportunities for diversifica- tion of the clinician scientific workforce.

青光眼治疗中一个尚未得到满足的主要需求是内科或外科手术降低眼压是唯一的 临床批准的治疗。但视力无法恢复，因为视网膜神经节细胞(RGC)丢失是不正确的。 说得通。改进治疗的知识差距包括如何实现神经保护，即预防视网膜节细胞 从死亡，或者，使用基于细胞的疗法来重新生长或替换。给药途径、剂量和不良反应 这些影响限制了神经保护和细胞移植的临床应用。研究一种新的治疗方法 细胞外小泡(EVS)，来自干细胞的具有生物活性的直径50-150 nm的纳米颗粒， 该提案填补了一项空白，迫切需要开发新的治疗方法来防止RGC死亡和视力 青光眼患者的损失。EVS是一种潜在的临床可用手段，可预防RGC、轴突和 视觉功能丧失，减少青光眼的兴奋性毒性和炎性成分。我们的中央 假设电动汽车可以被设计和优化，以特别针对RGC作为精确度的基础 治疗青光眼，并最终治疗其他视网膜疾病。我们建议将工程电动汽车作为一种新型汽车进行测试 无细胞意味着专门针对视网膜节细胞的神经保护并填补目前的知识空白 防止EVS用于视网膜疾病的临床翻译。我们的具体目标是目标1：确定时间进程 和调节EVS在玻璃体和视网膜中的分布的因素，并优化EV的输送以 视网膜。目标2：开发和优化专门针对RGC的新型工程电动汽车。成功的COM- 在玻璃体内注射后，去除AIM 1将优化EVS到视网膜的输送。《目标2》将指导 电动汽车的管理，以产生创新的，具体的，有针对性的交付到RGC，允许专门化 青光眼主要病理生理部位的治疗。这些目标的实现将为 通过优化给药和特定RGC靶向的EVS，开发使用EVS的青光眼治疗药物。 这项研究提供了通过开发安全、有效和成本效益高的恢复方法来挽救视力的前景 或防止青光眼患者失明。这一贡献预计将是巨大的，因为这些 研究将为开发EVS作为青光眼的治疗方法提供基础，无论是主要恢复RGC功能 和轴突生长，或优化现有的治疗方法，如RGC移植。创新的功能是细胞- 青光眼的免费治疗，用于特定RGC作用的新型靶向EVS，以及用于EVS的新型递送材料。 多样性副刊建议对本科生进行数据收集和分析方面的培训， 批判性地回顾文献，设计实验，撰写研究报告。这名学生将参与其中 在暑假和学年期间与该项目合作。我们的目标是利用这种体验来增加 学生对临床研究的兴趣，并最终帮助确保更多的多元化机会- 临床医生科学队伍的地位。