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

• 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
• 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

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.

摘要 视网膜神经节细胞（RGC）轴突的再生和重新连接不良是视网膜神经节细胞再生的主要障碍。 治疗眼外伤和包括青光眼在内的疾病。目前还没有治疗方法可以修复 视神经受损后的反应我们的新研究发现， 具有很高的再生能力。此外，我们现在发现了以前未被发现的 不同脂质促进轴突生长的能力。在目标1中，我们将使用高内容筛选 并功能性地测试各种候选基因促进神经突生长的能力。在Aim中 2，我们将测定RGCs中的脂质分布，并在功能上测试促进神经突生长的作用 选择的脂质。目的三：利用活体视神经损伤模型，确定RGC轴突的形态 再生，接受各种处理。确定进一步增加RGC的新靶点 轴突再生到大脑代表了一个关键的未来研究。从这些获得的结果 研究将提供宝贵的信息，开发未来的治疗方法，以修复退化的 视神经