Novel Targets to Promote RGC Axon Regeneration: Insights from Unique RGC Cohorts

促进 RGC 轴突再生的新目标：来自独特 RGC 队列的见解

基本信息

批准号：
9340195
负责人：
Sanjoy K Bhattacharya
金额：
$ 67.54万
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：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9340195
关键词：
Adult Affect Axon Bioinformatics Biological Process Brain Candidate Disease Gene Cell Death Cells Communication Data Dependovirus Disease Etiology Eye Future Genes Genetic Genomics Glaucoma Glycosphingolipids Grant Growth In Vitro Inborn Genetic Diseases Inflammatory Injury Investigation Ions Ischemia Label Lipids Membrane Methods Minor Modeling Mus Natural regeneration Nerve Nerve Crush Neurites Neurons Optic Nerve Optic Nerve Injuries Pathology Phenotype Photosensitivity Population Proteomics RNA Interference Recovery of Function Regulation Research Retinal Ganglion Cells Role Sphingolipids Testing Textiles Three-Dimensional Imaging Time Transgenic Mice Trauma Vesicle Visual analytical tool axon growth axon injury axon regeneration cohort differential expression functional restoration improved in vivo in vivo Model injured insight knock-down melanopsin membrane biogenesis nerve supply neurite growth neuronal growth novel optic nerve disorder optic nerve regeneration overexpression postnatal regenerative repaired screening transcriptome sequencing

项目摘要

ABSTRACT Poor regeneration and reconnection of retinal ganglion cell (RGC) axons is a major obstacle for treating ocular trauma and diseases including glaucoma. There are as yet no therapies to repair optic nerve once the damage is done. Our new studies have discovered cohorts of RGCs that have a very high regenerative capacity. Furthermore, we now uncover previously unrecognized ability of distinct lipids to promote axon growth. In Aim 1, we will use High Content Screening and functionally test various candidate genes for their ability to promote neurite growth. In Aim 2, we will determine lipid profiles in RGCs, and functionally test neurite growth-promoting effects of select lipids. In Aim 3, we will use in vivo optic nerve injury model to determine RGC axon regeneration receiving various treatments. Identifying novel targets that further increase RGC axon regeneration to the brain represents a critical future study. Results obtained from these studies will provide invaluable information on developing future therapies to repair degenerated optic nerve.

抽象的视网膜神经节细胞（RGC）轴突的再生和重新连接不良是主要障碍治疗包括青光眼在内的眼部创伤和疾病。尚无修复疗法损伤造成的视神经。我们的新研究发现了RGC的同类具有很高的再生能力。此外，我们现在发现以前未被认可不同脂质促进轴突生长的能力。在AIM 1中，我们将使用高内容筛选并在功能上测试各种候选基因促进神经突生长的能力。目标 2，我们将确定RGC中的脂质谱，并在功能上测试神经突增长效应选择的脂质。在AIM 3中，我们将使用体内视神经损伤模型来确定RGC轴突再生接受各种治疗。确定新的目标，以进一步增加RGC 轴突对大脑的再生代表了一项关键的未来研究。从这些结果获得的结果研究将提供有关开发未来疗法以修复退化的宝贵信息视神经。