Disease and Continuous Myofiber Remodeling in EOM

EOM 中的疾病和连续肌纤维重塑

• 批准号: 6622930
• 负责人: LINDA K. MCLOON
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622930
• 关键词: animal tissue; apoptosis; clinical research; electron microscopy; extraocular muscle; eye coordination disorder; eye movement disorders; eye surgery; human tissue; immunocytochemistry; laboratory rabbit; light microscopy; mature animal; myofibrils; myogenesis; regeneration

DESCRIPTION: (Applicant's Abstract) Extraocular muscles (EOM) are spared or preferentially involved in various skeletal muscle diseases. We propose a novel and controversial alternative mechanism that may form the basis for the differences between extraocular muscles and limb skeletal muscles. We have strong preliminary evidence to suggest that there is ongoing, continuous myofiber remodeling in the adult extraocular muscles. This would involve both myogenic and apoptotic components. These conclusions are based on 4 lines of evidence. In this proposal we are asking questions to confirm our original observations. We have shown that the EOM continue to express cells positive for myogenic regulatory factors, such as myoD. Activated satellite cells are always present in adult EOM. BrdU labeling experiments using both 2 week and 4 week continuous labeling protocols followed by various brdU-free periods, a protocol that labels dividing cells, demonstrated mature myofibers with brdU-positive nuclei within them. Our working hypothesis is that there are mechanisms present in adult EOM that allow continuous satellite cell activation and division, resulting in either continuous remodeling of existing myofibers by fusion of new myoblasts with existing adult myofibers or formation of entirely new myofibers by the fusion of myoblasts with each other. This proposal asks the following questions: What are the mechanisms of myofiber remodeling in adult EOM? What is the time course and extent of fiber remodeling? What role does apoptosis play in myofiber remodeling and by what mechanism? How do surgical and chemodenervation manipulations simulating strabismus treatments cause changes in myofiber remodeling that may be affecting long-term surgical outcomes? The ability of adult EOM to continuously remodel provides a wealth of testable hypotheses for some long-standing enigmas involving the EOM and their preferential sparing or involvement in various muscle diseases. Ultimately, we hope to use this information to develop new therapeutic strategies.for the treatment of strabismus and other ocular and non-ocular muscle diseases.

描述：（申请人的摘要）外部肌肉（EOM）幸免或 优先涉及各种骨骼肌疾病。我们提出了一本小说 以及有争议的替代机制，这可能构成 外部肌肉和肢体骨骼肌之间的差异。我们有 有力的初步证据表明，存在持续的，连续的 成人眼外肌肉中的肌纤维重塑。这两个都涉及 肌原和凋亡成分。这些结论基于4行 证据。在此提案中，我们提出问题以确认我们的原始 观察。我们已经表明，EOM继续表达细胞的阳性 肌源性调节因素，例如myod。活化的卫星电池总是 在成人EOM中存在。使用2周和4周的BRDU标记实验 连续标记协议，然后是各种无BRDU期间，一个协议 标记分裂细胞，以BRDU阳性证明成熟的肌纤维 其中的核。我们的工作假设是存在机制 在允许连续卫星细胞激活和分裂的成年EOM中， 通过融合而导致现有肌纤维的连续重塑 与现有的成年肌纤维或全新形成的新成肌细胞 肌纤维通过肌细胞的融合彼此融合。该提议问 以下问题：成人肌纤维重塑的机制是什么 eom？纤维重塑的时间过程和程度是什么？有什么角色 凋亡在肌纤维重塑中发挥作用，并通过什么机制？如何手术 和化学修饰操作模拟斜视治疗导致 可能会影响长期手术的肌纤维重塑的变化 结果？成人EOM连续改造的能力提供了丰富的丰富 可检验的假设，用于一些涉及EOM及其的长期谜团 优先保留或参与各种肌肉疾病。最终，我们 希望使用这些信息来制定新的治疗策略。 治疗斜视和其他眼和非眼肌疾病。