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：
8502088
负责人：
Alon Kahana
金额：
$ 37.99万
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/8502088
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 6 对眼外肌 (EOM) 对眼球运动进行复杂的控制。先天性和后天性斜视会导致双眼输入错位，从而分别导致弱视或复视。斜视手术是目前的标准治疗方法，但手术通常会导致纤维化和肌肉功能受损。该研究计划的中心概念是肌肉再生与手术相结合，将比单独的肌肉手术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，并利用它们开发治疗斜视疾病的新治疗方法。哺乳动物修复受损 EOM 的能力有限，而斑马鱼在再生复杂组织（包括 EOM）方面特别有效。我们的策略是利用斑马鱼来识别和表征可以驱动 EOM 再生的生物机制。我们最近鉴定了 EOM 再生的遗传调节因子的一个子集。我们的数据表明，斑马鱼的 EOM 再生依赖于现有心肌细胞的受调节重编程，而不是内在的干（卫星）细胞，这表明斑马鱼如此擅长 EOM 再生的生物学基础。该项目旨在利用斑马鱼建立对肌肉再生的机制理解，并重点关注可作为潜在治疗靶点的过程，例如细胞凋亡、自噬和细胞外基质重塑的调节。