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3D visualization and Investigation of Retinal Axon Regeneration

视网膜轴突再生的 3D 可视化和研究

基本信息

批准号：
10577812
负责人：
KEVIN Kyung PARK
金额：
$ 38.38万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10577812
关键词：
3-Dimensional Adopted Adult Axon Brain Cell Nucleus Cells Central Nervous System Ciliary Neurotrophic Factor Confocal Microscopy Disease Eye Injuries Failure Fluorescence Microscopy Freezing Future Genes Genetic Transcription Goals Heterogeneity Imaging Techniques Immunoprecipitation Injury Investigation Label Laboratories Lesion Light Mammals Masks Mechanics Methodology Molecular Mus Natural regeneration Nerve Degeneration Optic Nerve Optics Organ Population Proteins Protocols documentation Recovery of Function Regenerative capacity Reporting Resistance Retina Retinal Ganglion Cells Shapes Solvents Stains THBS1 gene Techniques Testing Three-Dimensional Imaging Thrombospondins Time Tissues Trauma Travel Vision Visualization assault axon injury axon regeneration cell type cellular imaging central nervous system injury experimental study improved in vivo injured insight neuronal cell body optic nerve disorder overexpression receptor reconstruction regenerative reinnervation repaired response retinal axon retinal ganglion cell regeneration screening single nucleus RNA-sequencing single-cell RNA sequencing syndecan three-dimensional visualization transcriptome sequencing transcriptomics unpublished works

项目摘要

3D Visualization and Investigation of Retinal Axon Regeneration Poor regeneration of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and optic neuropathies. There are yet no therapies to repair damaged optic nerve. Our previous studies have demonstrated that modulation of distinct genes promotes long distance regeneration of some RGC axons in adult mice. However, promoting axons not only to regenerate into the lesion, but to travel long distances, and to reconnect with their central targets is still a major challenge. In fact, we and others have reported that only a few axons reinnervate the brain. It is unclear what cellular and molecular factors contribute to the limited pathfinding, and the lack of target re-innervation. The overall goal of this proposal is to; i) identify effective approaches that promote regeneration and reconnection of RGC axons, ii) optimize three dimensional imaging techniques to examine subtype-specific regeneration, and iii) assess the genes that are regulated by the regenerative- promoting factors using single nucleus RNA sequencing. Identifying strategies to further increase regeneration and re-innervation in the brain represents critical future studies. Results obtained from these studies will provide invaluable information on developing future therapies to repair degenerated optic nerve after trauma or in diseases.

视网膜轴突再生的三维可视化研究视网膜神经节细胞轴突再生不良是眼外伤和视神经损伤治疗的主要障碍。神经病。目前还没有修复受损视神经的治疗方法。我们之前的研究已经证明差异基因的调节促进了一些RGC轴突的远距离再生成年小鼠。然而，促进轴突不仅再生到病变中，而且还能长距离传播，并与他们的核心目标重新建立联系仍然是一个重大挑战。事实上，我们和其他人报告说，只有少数人轴突对大脑进行再神经支配。目前还不清楚是什么细胞和分子因素导致了有限的路径发现，以及缺乏靶神经的重新支配。这项提案的总体目标是：i)找出有效的办法，促进RGC轴突再生和重新连接，II)优化三维成像技术，以检查特定亚型的再生，以及iii)评估由再生- 促进因子采用单核RNA测序。确定进一步增加再生的战略而大脑中的重新神经支配代表着关键的未来研究。从这些研究获得的结果将提供关于开发未来治疗方法以修复创伤后或... 疾病。