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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：
10380861
负责人：
KEVIN Kyung PARK
金额：
$ 37.22万
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 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10380861
关键词：
3-Dimensional Adopted Adult Axon Brain Cell Nucleus Cells 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 Neuraxis Optic Nerve Optics Organ Population Proteins Protocols documentation Recovery of Function Regenerative capacity Reporting Resistance Retina Retinal Ganglion Cells Shapes Small Nuclear RNA Solvents Stains THBS1 gene Techniques Testing Three-Dimensional Imaging Time Tissues Trauma Travel Vision Visualization assault axon injury axon regeneration cell type cellular imaging central nervous system injury cohesion experimental study improved in vivo injured insight nerve supply neuronal cell body optic nerve disorder overexpression receptor reconstruction regenerative reinnervation repaired response retinal axon retinal ganglion cell regeneration single-cell RNA sequencing three-dimensional visualization transcriptome sequencing transcriptomics unpublished works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（retinal ganglion cell，RGC）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治疗方法来修复受损的视神经。我们以往的研究表明不同基因的调节促进了一些RGC轴突的长距离再生，成年老鼠然而，促进轴突不仅再生到病变，但旅行长距离，与其中心目标重新建立联系仍然是一项重大挑战。事实上，我们和其他人报告说，只有少数轴突重新支配大脑目前还不清楚是什么细胞和分子因素导致了有限的寻路，以及缺乏目标神经再支配。本建议的总体目标是：（一）确定有效的方法，促进RGC轴突的再生和重新连接，ii）优化三维成像技术，检查亚型特异性再生，和iii）评估由再生- 使用单核RNA测序的促进因子。确定进一步增加再生的战略大脑中的神经再生代表着未来的重要研究。这些研究的结果将提供宝贵的信息，发展未来的治疗，以修复退化的视神经后，创伤或疾病