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）眼外肌（EOM）不受损害或 优先参与各种骨骼肌疾病。我们提议写一本小说 和有争议的替代机制，可能构成 眼外肌和肢体骨骼肌之间的差异。我们有 强有力的初步证据表明，存在持续的、连续的 成人眼外肌的肌纤维重塑。这将涉及双方 生肌和凋亡成分。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提案 观察。我们已经证明 EOM 继续表达阳性细胞 肌源性调节因子，例如 myoD。卫星细胞始终处于激活状态 存在于成人 EOM 中。使用 2 周和 4 周进行 BrdU 标记实验 连续标记方案，随后是各种无 brdU 期，一个方案 标记分裂细胞，显示出 brdU 阳性的成熟肌纤维 它们内部的原子核。我们的工作假设是存在机制 在成人 EOM 中，允许卫星细胞持续激活和分裂， 通过融合导致现有肌纤维的连续重塑 新的成肌细胞与现有的成体肌纤维或形成全新的 成肌细胞相互融合形成肌纤维。该提案要求 以下问题：成人肌纤维重塑的机制是什么 停产？纤维重塑的时间进程和程度是多少？有什么作用 细胞凋亡在肌纤维重塑中发挥作用，其机制是什么？怎样做手术 和化学去神经操作模拟斜视治疗的原因 肌纤维重塑的变化可能影响长期手术 结果？成人EOM不断重塑的能力提供了丰富的 一些涉及 EOM 及其相关问题的长期谜团的可检验假设 优先避免或参与各种肌肉疾病。最终，我们 希望利用这些信息来开发新的治疗策略。 治疗斜视和其他眼部和非眼部肌肉疾病。