Promoting optic nerve and retinofugal pathway regeneration

促进视神经和视网膜离断通路再生

• 批准号: 9338034
• 负责人: Andrew D Huberman
• 金额: $ 39.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338034
• 关键词: Address; Adult; Alzheimer' s Disease; Animals; Axon; Axotomy; Back; Blindness; Brain; Cell Nucleus; Clinical; Collection; Data; Disease; Eye; FRAP1 gene; Genetic; Glaucoma; Goals; Growth; Health; Home environment; Human; In Vitro; Injury; Knowledge; Label; Lead; Molecular; Mus; Natural regeneration; Nerve Crush; Neurons; Optic Nerve; Output; Pathway interactions; Pattern; Photic Stimulation; Play; Property; Recovery of Function; Research; Resolution; Retinal; Retinal Degeneration; Retinal Ganglion Cells; Role; Signal Transduction; Specificity; Spinal Cord; Stimulus; Structure; Synapses; System; Testing; Vision; Visual; Visual Pathways; Visual system structure; axon growth; axon regeneration; behavior measurement; cell growth; cell type; experience; experimental study; in vivo regeneration; injured; mTOR inhibition; novel; optic nerve disorder; programs; reconstruction; repaired; response; response to injury; restoration; selective expression; tool

Project Summary/Abstract The overall goal of this research program is to understand how to regenerate mammalian central visual pathways. This proposal specifically focuses on the question of how to regenerate projections from output neurons of the eye, retinal ganglion cells (RGCs) to their targets in the brain (collectively referred to `retinofugal pathway')- a circuit absolutely essential vision. Significant progress has recently been made in identifying molecular programs capable of triggering some RGC axon regeneration. The next crucial milestones for the field are to discover ways to increase the number RGC axons that regenerate and the distance they regro. It is also crucially important to determine whether regenerating RGCs can find and reconnect to the correct targets, such visual capacities return. The three major aims of this proposal are to: 1) test the hypothesis that specific forms of visual stimulation can enhance the number and distance of RGC regenerating axons 2) test the hypothesis that combining visual stimulation with molecular triggers of RGC axon growth can cause RGC axons to regrow long distances back into the brain and 3) determine whether regenerating RGCs are capable of pathfinding back to and re-connecting to their appropriate targets, as well as avoiding targets incorrect for their function. Results from these experiments should lead to new understanding of how mammalian visual circuits can be replenished in response to injury and pave the way for the cultivation of tools applicable to humans suffering from vision loss.

项目总结/摘要 这项研究计划的总体目标是了解如何再生 哺乳动物的中央视觉通路这一建议特别侧重于以下问题： 如何从眼睛的输出神经元，视网膜神经节细胞 视网膜神经节细胞（RGCs）与其脑中的靶点（统称为“离视网膜途径”）- a 电路绝对必要的视觉。最近在以下方面取得了重大进展： 鉴定能够触发某些RGC轴突再生的分子程序。的 该领域的下一个重要里程碑是找到增加研究资助委员会人数的方法 轴突的再生和它们再生的距离同样至关重要的是， 确定再生RGC是否可以找到并重新连接到正确的目标， 这种视觉能力恢复了。这项建议的三个主要目的是：1）测试 假设特定形式的视觉刺激可以增加数量， RGC再生轴突的距离2）测试结合视觉的假设 用RGC轴突生长的分子触发物刺激可以引起RGC轴突再生 长距离返回大脑和3）确定再生RGC是否 能够寻路返回并重新连接到适当的目标，以及 避免不符合其功能的目标。这些实验的结果应该会导致 对哺乳动物视觉回路如何在反应中得到补充的新认识 伤害和铺平道路的种植工具适用于人类遭受 视力丧失