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: 7896210
• 负责人: James G. Patton
• 金额: $ 22.7万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7896210
• 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; Methodology; MicroRNAs; Modeling; Mus; Natural regeneration; Neuroglia; Neurons; Nucleotides; Oligonucleotides; Pathway interactions; Patients; Pattern; Photoreceptors; Play; Process; RNA; Regulator Genes; Reporter; Repression; Retina; Retinal; Retinal Degeneration; Role; Signal Transduction; Testing; Translations; Vision; Zebrafish; blastema; functional restoration; gain of function; human disease; light treatment; loss of function; progenitor; 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）：在过去几年中发现了许多非编码RNA，其中最佳特征是21-23个核苷酸RNA的家族，称为microRNAS（miRNA）。脊椎动物基因组编码了数百个miRNA，这些miRNA主要是通过抑制翻译来调节基因表达的。尽管在阐明执行miRNA功能的加工途径和效应子络合物方面取得了进展，但对于由miRNA控制的确切靶标mRNA知之甚少。我们一直在使用斑马鱼作为模型系统来识别miRNA靶标。在这里，我们建议进行微阵列，以识别斑马鱼视网膜再生期间差异表达的miRNA，然后在功能上测试此类miRNA的参与，以鉴定控制视网膜再生的关键基因和调节级联。 公共卫生相关性：对于人类而言，寿命增加将增加患有一种或多种眼部疾病的患者的数量。目前，失明或视力受损会影响超过300万美国人，但预计到2020年，这一数字将增加到超过500万（Opthalmology的档案，2004年4月）（Ferris III和Tielsch，2004年）。人眼的许多疾病都涉及光感受器细胞的丧失，损害或变性，但与鱼类相反，再生几乎没有再生。该提案试图了解视网膜再生的机制，希望理解允许这种再生的信号可以识别恢复或保留感光体的治疗靶标。