Analysis of miRNA Function During Eye Development and Retinal Regeneration

眼睛发育和视网膜再生过程中 miRNA 功能分析

• 批准号: 8039909
• 负责人: James G. Patton
• 金额: $ 18.69万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039909
• 关键词: Affect; American; Antibodies; Archives; Biological Models; Blindness; Cells; Circadian Rhythms; Complex; Disease; Eye; Eye Development; Eye diseases; Family; Fishes; Functional RNA; Gene Expression; Genes; Health; Human; Incidence; Light; Longevity; Mediating; Messenger RNA; Methodology; MicroRNAs; Modeling; Mus; N-Methylaspartate; Natural regeneration; Neuroglia; Nucleotides; Oligonucleotides; Pathway interactions; Patients; Pattern; Photoreceptors; Play; Process; RNA; Regulator Genes; Reporter; Repression; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Role; Signal Transduction; Testing; Translations; Vision; Zebrafish; blastema; functional restoration; gain of function; human disease; light treatment; loss of function; nerve stem cell; programs; public health relevance; repaired; research study; retinal damage; retinal neuron; retinal regeneration; stem; therapeutic target; tool; vertebrate genome

DESCRIPTION (provided by applicant): A number of non-coding RNAs have been discovered in the last few years, the best characterized of which are a family of 21-23 nucleotide RNAs referred to as microRNAs (miRNAs). Vertebrate genomes encode hundreds of miRNAs that regulate gene expression at the post-transcriptional level, primarily through repression of translation. Despite progress in elucidating the processing pathways and effector complexes that carry out miRNA function, precious little is known about the exact target mRNAs controlled by miRNAs. We have been using zebrafish as a model system to identify miRNA targets. Here, we propose to perform microarrays to identify miRNAs that are differentially expressed during zebrafish retinal regeneration and then functionally test the involvement of such miRNAs to identify key genes and regulatory cascades that control retinal regeneration. PUBLIC HEALTH RELEVANCE: For humans, increased life span will increase the numbers of patients suffering from one or more eye diseases. Currently, blindness or impaired vision affects over 3 million Americans but that number is expected to increase to over 5 million just by 2020 (Archives of Opthalmology, April, 2004) (Ferris III and Tielsch, 2004). Many diseases of the human eye involve loss, damage or degeneration of photoreceptor cells but in contrast to fish, regeneration is mostly absent. This proposal seeks to understand the mechanisms of retinal regeneration in the hopes that understanding the signals that allow such regeneration might identify therapeutic targets to restore or preserve photoreceptors.

描述（由申请人提供）：过去几年中发现了许多非编码RNA，其中最具特征的是被称为microRNA（miRNA）的21-23个核苷酸RNA家族。脊椎动物基因组编码数百种 miRNA，这些 miRNA 主要通过抑制翻译来在转录后水平调节基因表达。尽管在阐明执行 miRNA 功能的加工途径和效应复合物方面取得了进展，但人们对 miRNA 控制的确切靶 mRNA 知之甚少。我们一直使用斑马鱼作为模型系统来识别 miRNA 靶点。在这里，我们建议进行微阵列来识别斑马鱼视网膜再生过程中差异表达的 miRNA，然后对此类 miRNA 的参与进行功能测试，以确定控制视网膜再生的关键基因和调控级联。 公共卫生相关性：对于人类来说，寿命的延长将增加患有一种或多种眼部疾病的患者数量。目前，失明或视力受损影响着超过 300 万美国人，但预计到 2020 年这一数字将增加到超过 500 万（眼科档案馆，2004 年 4 月）（Ferris III 和 Tielsch，2004 年）。人眼的许多疾病都与感光细胞的损失、损伤或退化有关，但与鱼类不同的是，感光细胞大多不存在再生。该提案旨在了解视网膜再生的机制，希望了解允许这种再生的信号可以确定恢复或保护光感受器的治疗靶点。