Neuronal Development, Injury and Repair in the Retina

视网膜神经元发育、损伤和修复

• 批准号: 8717662
• 负责人: Peter F Hitchcock
• 金额: $ 50.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8717662
• 关键词: Adult; Biology; Birth; Blindness; Brain; Cell Cycle; Cell Transplants; Cells; Cessation of life; Data; Development; Disease; Event; Extracellular Matrix; Fishes; Funding; Genetic; Goals; Growth Factor; Growth Factor Gene; Health; Human; Injury; Knowledge; Literature; Mediating; Microglia; Mitotic; Molecular; Natural regeneration; Nerve Regeneration; Nerve Tissue; Nervous system structure; Neuraxis; Neurons; Outcome; Pathway interactions; Photoreceptors; Play; Progranulin; Regulation; Research; Retina; Retinal; Role; Signal Transduction; Signaling Molecule; Source; Stem cells; Testing; Therapeutic Uses; Tissues; Transplantation; Vision; Withdrawal; Work; Zebrafish; abstracting; adult stem cell; base; cell type; driving force; injured; injury and repair; killings; knowledge of results; midkine; nerve stem cell; neural circuit; neurogenesis; neuron development; photoreceptor progenitor; progenitor; programs; receptor; regenerative; relating to nervous system; repaired; retinal neuron; stem; teleost; transcription factor

Project Summary/Abstract Injuries or diseases that kill retinal neurons and receptors block vision at it source. The resulting blindness is permanent. The inability to repair in the retina is a hallmark of the human central nervous system; neurons that die are not replaced and functions that are lost are not recovered. This bleak outcome is a driving force for research on neural stem cells and the field of regeneration biology. The long-term objective of this project is to elucidate the mechanisms that regulate the birth, death and regeneration of neurons and photoreceptors in the vertebrate retina. This program of research utilizes the zebrafish, because the fish retina is the only vertebrate CNS tissue where intrinsic stem cells can regenerate a single neuronal type that integrates into an existing circuit or can regenerate all cell types that completely restore the original tissue. Thus, investigating stem cell-based neuronal and photoreceptor regeneration in the teleost retina will advance our knowledge of mechanisms that govern the ability of intrinsic stem and progenitor cells to restore neural circuits in the injured brain. The resulting knowledge will guide the therpeutic use of transplanted stem and progenitor cells to treat retinal injuries, blindness and disease. Three Specific Aims are proposed, each directed toward revealing mechanisms that regulate the genesis and regeneration of photoreceptors. Specific Aim 1 will investigate the function of the bHLH transcription factor, NeuroD, in both the developing and regenerating retina. Specific Aim 2 will test the hypothesis that microglia play a neurogenic role during photoreceptor regeneration. Specific aim 3 will test the hypothesis that the soluble growth factor, midkine-a, controls aspects of retinal development in larval zebrafish and photoreceptor regeneration in adults. Together these specific aims represent a focused and integrated research program to test specific hypotheses of the biology and regulation of retinal development and neuronal regeneration in the vertebrate nervous system.

项目概要/摘要 杀死视网膜神经元和受体的损伤或疾病会从根源上阻碍视力。这 由此造成的失明是永久性的。视网膜无法修复是该病的一个标志 人体中枢神经系统；死亡的神经元不会被替换，其功能也会被替换 丢失的无法找回。这种惨淡的结果是神经干研究的驱动力 细胞和再生生物学领域。该项目的长期目标是 阐明调节神经元的诞生、死亡和再生的机制 和脊椎动物视网膜中的光感受器。该研究计划利用 斑马鱼，因为鱼的视网膜是唯一具有内在茎的脊椎动物中枢神经系统组织 细胞可以再生单个神经元类型，该神经元类型可以整合到现有的电路中，或者可以 再生所有细胞类型，完全恢复原始组织。因此，调查 硬骨鱼视网膜中基于干细胞的神经元和光感受器再生将 增进我们对控制内在干细胞能力的机制的了解 祖细胞可以恢复受损大脑中的神经回路。由此产生的知识 将指导移植干细胞和祖细胞治疗视网膜的治疗用途 受伤、失明和疾病。提出了三个具体目标，每个目标都有针对性 揭示调节发生和再生的机制 光感受器。具体目标 1 将研究 bHLH 转录的功能 NeuroD 因子在视网膜的发育和再生中发挥作用。具体目标2将测试 小胶质细胞在光感受器再生过程中发挥神经源性作用的假设。 具体目标 3 将检验可溶性生长因子 midkine-a 控制的假设 幼虫斑马鱼的视网膜发育和光感受器再生的方面 成年人。这些具体目标共同代表了一项集中且​​综合的研究 测试视网膜发育的生物学和调节的具体假设的程序 和脊椎动物神经系统中的神经元再生。