Molecular mechanisms of retinogeniculate circuit formation

视网膜原路形成的分子机制

• 批准号: 9549105
• 负责人: MICHAEL A FOX
• 金额: $ 38.27万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9549105
• 关键词: Affect; American; Anatomy; Axon; Blindness; Brain; Brain region; Candidate Disease Gene; Cell Nucleus; Cells; Coculture Techniques; Complex; Cues; Data; Dendrites; Dependovirus; Development; Disease; Dorsal; Economic Burden; Electrophysiology (science); Eye diseases; Fostering; Funding; Genes; Glaucoma; Goals; Growth; Histologic; IGF1R gene; Immunohistochemistry; In Vitro; Individual; Injections; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Interneurons; Knowledge; Label; Lateral Geniculate Body; Leucine-Rich Repeat; Mind; Molecular; Molecular Genetics; Mus; National Eye Institute; Natural regeneration; Nerve; Nerve Degeneration; Neuroglia; Neurons; Patients; Persons; Phenotype; Physiological; Population; Proteins; Recombinant IGF-I; Recombinants; Reporter; Research; Retina; Retinal; Retinal Ganglion Cells; Role; Signal Transduction; Somatomedins; Swimming; Synapses; Techniques; Testing; Thalamic structure; Transgenic Organisms; Validation; Viral; Vision; Visual; Visual impairment; Work; age related; base; cost; design; effective therapy; experimental study; mutant; novel; regenerative therapy; relating to nervous system; response; retinal axon; retinogeniculate; social; superior colliculus Corpora quadrigemina; synaptogenesis; transcriptome sequencing; viral rescue; visual information

Developmental and age-related disorders that affect vision impart a major social and economic burden on the US economy. Many of these disorders specifically affect neurons that connect the retina (i.e., retinal ganglion cells [RGCs]) information to the brain. The most common of these disorders is glaucoma, a progressive neurodegenerative eye disorder that is the leading cause of irreversible blindness in the US. Currently, 3 million Americans are living with glaucoma, costing the US economy nearly 3 billion dollars each year. Glaucoma is not the only disorder that impacts RGCs. Currently there are no effective treatments for patients with glaucoma. In response to this unmet need, NEI has issued a goal of gaining new knowledge that will contribute to the development of regenerative therapies aimed at restoring connections between the retina and brain. To accomplish this goal, we need a better understanding of the mechanisms that drive the formation of these connections during normal development. Over the past 5 years, we investigated the mechanisms that drive the growth of retinal axons into appropriate target regions of brain. During this work, we discovered that retinal synapses in the dorsal lateral geniculate nucleus (dLGN) are anatomically and functionally distinct from retinal synapses in all other retino-recipient regions. Because these synapses are crucial for transmitting visual information to cortex, understanding mechanisms of their formation is essential for restoring subcortical visual circuit function. With this in mind, the objective of this application aims to identify target-derived cues responsible for the unique development of retinogeniculate synapses in dLGN. Preliminary experiments identified Insulin-like Growth Factor 1 (IGF1) and Leucine-Rich Repeat Transmembrane Neuronal Protein 1 (LRRTM1) as two synaptogenic cues expressed in dLGN. Here will will use molecular, genetic, anatomical and physiological approaches to assess roles of these molecules in retinogeniculate circuit formation.

影响视力的发育障碍和年龄相关障碍给老年人带来了重大的社会和经济负担。 美国经济。这些疾病中的许多特别影响连接视网膜的神经元（即，视网膜神经节 细胞（RGC）的信息传递到大脑。这些疾病中最常见的是青光眼， 神经退行性眼病是美国不可逆失明的主要原因。现有3 青光眼是一种常见的眼病，每年给美国经济造成近30亿美元的损失。 青光眼不是影响RGC的唯一疾病。目前还没有有效的治疗方法 青光眼为了应对这一未满足的需求，NEI发布了一个目标，即获得新知识， 有助于再生疗法的发展，旨在恢复视网膜和视网膜之间的连接， 个脑袋为了实现这一目标，我们需要更好地了解驱动形成的机制。 在正常发育过程中。在过去的5年里，我们研究了 驱动视网膜轴突生长到大脑的适当目标区域。在这项工作中，我们发现， 背外侧膝状体核（dLGN）中的视网膜突触在解剖学和功能上不同于 在所有其他视网膜受体区域的视网膜突触。因为这些突触对于传递视觉信号至关重要 信息传递到皮层，了解其形成机制对于恢复皮层下视觉至关重要 电路功能考虑到这一点，本申请的目的在于识别目标源线索 负责dLGN中retinogeniculate突触的独特发育。初步实验 已鉴定的胰岛素样生长因子1（IGF 1）和富含亮氨酸的重复跨膜神经元蛋白1 （LRRTM1）作为dLGN中表达的两种突触发生线索。这里将使用分子，遗传，解剖和 生理学方法评估这些分子在视网膜神经回路形成中的作用。