STEM CELL-BASED THERAPIES FOR AGE-RELATED MACULAR DEGENERATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 老年性黄斑变性(AMD)是老年人最常见的致盲原因，但缺乏治疗方法。这项转化研究计划的目标是使用干细胞替代疗法保护和恢复AMD患者的视力。具体目标1是培养和鉴定潜在的治疗性细胞类型，包括前脑来源的人神经干细胞和经过修饰的人神经干细胞，以分泌特定的神经保护因子，包括胶质衍生生长因子。具体目的2是将这些细胞移植到视网膜退化的啮齿动物模型的眼睛中，以测试供体细胞的存活率、功能和形态挽救的证据以及治疗并发症的风险。具体目标3是确定和优化细胞给药程序和剂量，然后评估恒河猴的安全性和生物分布。我们将首先研究正常眼睛，然后测试我们独特的恒河猴老年性黄斑变性模型的疗效。这项研究的成功完成将为人类临床试验铺平道路，这些试验可能会对这种主要致盲疾病的临床结果产生相当大的影响。在过去的一年里，我们完成了一项研究，证明了干细胞移植到猴子视网膜的可行性和安全性，并证明了干细胞移植显著减缓了遗传性视网膜变性转基因小鼠的视力丧失和形态变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly, but treatments are lacking. The goal of this translational research program is to protect and restore vision in AMD using stem cell replacement therapy. Specific Aim 1 is to culture and characterize potentially therapeutic cell types, including forebrain-derived human neural stem cells and human neural stem cells modified to secrete specific neuroprotective factors, including glial derived growth factor. Specific Aim 2 is to transplant these cells to the eyes of rodent models with retinal degenerations to test donor cell survival, evidence of functional and morphological rescue and risk of treatment complications. Specific Aim 3 is to define and optimize the cell delivery procedure and dosage and then evaluate safety and biodistribution in rhesus monkeys. Normal eyes will be studied first, followed by a test of efficacy in our unique rhesus monkey model of age-related macular degeneration. Successful completion of this research will pave the way towards human clinical trials that could have considerable impact on the clinical outcomes for this major blinding condition. In the past year we completed a study showing the feasibility and safety of stem cell transplantation to the monkey retina, and demonstrated that stem cell transplants significantly slowed vision loss and morphological changes in a transgenic mouse model of hereditary retinal degeneration.