A Zebrafish model of extraocular muscle regeneration.

眼外肌再生的斑马鱼模型。

基本信息

批准号：
8616762
负责人：
Alon Kahana
金额：
$ 37.23万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8616762
关键词：
Address Adherens Junction Adult Affect Amblyopia Apoptosis Apoptotic Automobile Driving Autophagocytosis Binocular Vision Biological Blindness Cadherins Cell Polarity Child Clinical Complex Data Diplopia E-Cadherin Event Extracellular Matrix Extracellular Matrix Proteins Eye Movements Failure Fibronectins Fibrosis Foundations Functional disorder Funding Genes Genetic Goals Human Inhibition of Apoptosis Injury Investigation Knowledge Lead Link Mammals Mediating Modeling Molecular Muscle Muscle Cells Muscle function Natural regeneration Neurologic Operative Surgical Procedures Population Process Protein Biosynthesis Proteins Proteolysis Regenerative Medicine Regulation Repression Research Role Sarcomeres Signal Transduction Strabismus Structure Testing Tissues Visual Work Zebrafish cell motility design functional outcomes improved insight muscle regeneration novel therapeutic intervention orbit muscle progenitor programs public health relevance repaired response to injury satellite cell standard of care stem therapeutic target twist protein

项目摘要

DESCRIPTION (provided by applicant): Binocular vision requires intricate control of eye movement by 6 pairs of extraocular muscles (EOMs). Congenital and acquired strabismus cause misaligned binocular input, which can lead to amblyopia or diplopia, respectively. Strabismus surgery is the current standard of care, but surgery commonly results in fibrosis and compromise in muscle function. The central concept of this research program is that muscle regeneration, in conjunction with surgery, will provide better functional outcomes than muscle surgery alone. Therefore, the long-term goal of the PI's research is to identify the molecular underpinnings that govern EOM regeneration and use them to develop novel therapeutic approaches for treating strabismic conditions. Mammals have only a limited ability to repair damaged EOMs, whereas zebrafish are particularly effective at regenerating complex tissues, including EOMs. Our strategy is to utilize zebrafish to identify and characterize the biological mechanisms that can drive EOM regeneration. We recently identified a subset of the genetic regulators of EOM regeneration. Our data reveal that EOM regeneration in zebrafish relies upon regulated reprogramming of extant myocytes rather than on intrinsic stem (satellite) cells, suggesting a biological foundation for the reason why zebrafish are so adept at EOM regeneration. The proposed project is designed to develop a mechanistic understanding of muscle regeneration using zebrafish, and focusing on processes that can serve as potential therapeutic targets, such as regulation of apoptosis, autophagy and extracellular matrix remodeling.

描述（由申请人提供）：双眼视觉需要通过6对眼外肌肉（EOM）进行复杂的眼睛运动。先天性和被收购的斜视引起的双眼输入不一致，这可能会导致弱视或复视。斜视手术是目前的护理标准，但是手术通常会导致肌肉功能的纤维化和妥协。该研究计划的核心概念是，肌肉再生与手术相比，与单独的肌肉手术相比，肌肉再生将提供更好的功能结果。因此，PI研究的长期目标是确定控制EOM再生的分子基础，并使用它们来开发用于治疗斜率疾病的新型治疗方法。哺乳动物仅修复受损EOM的能力有限，而斑马鱼在包括EOM在内的复杂组织中特别有效。我们的策略是利用斑马鱼来识别和表征可以驱动EOM再生的生物学机制。我们最近确定了EOM再生的遗传调节剂的子集。我们的数据表明，斑马鱼中的EOM再生依赖于调节现存的肌细胞而不是内在的茎（卫星）细胞的调节重编程，这表明生物学基础的基础是斑马鱼如此善于EOM再生的原因。拟议的项目旨在使用斑马鱼对肌肉再生进行机械理解，并专注于可以作为潜在治疗靶标的过程，例如调节凋亡，自噬和细胞外基质重塑。