Determinants of extraocular muscle function

眼外肌功能的决定因素

• 批准号: 7809255
• 负责人: Francisco H Andrade
• 金额: $ 3.52万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7809255
• 关键词: Academy; Address; Adult; Aerobic; Affect; Age; Aging; American; Biochemical; Biogenesis; Biological Assay; Biology; Boxing; Buffers; Calcium; Cell Respiration; Cells; Characteristics; Child; Chronic progressive external ophthalmoplegia; Clinical; Complex; Creatine Kinase; Data; Dependence; Development; Electron Transport; Eye; Eye Movements; Fatigue; Incidence; Knowledge; Life; Limb structure; Metabolic; Metabolic Pathway; Mitochondria; Mitochondrial Myopathies; Modeling; Motor; Muscle; Muscle Mitochondria; Muscle Proteins; Muscle function; Myosin ATPase; Neuromuscular Diseases; Ocular Motility Disorders; Pediatrics; Phenotype; Pilot Projects; Predisposition; Property; Protein Isoforms; Research Personnel; Resistance; Resolution; Sensory; Skeletal Muscle; Stereotyping; Strabismus; System; Testing; Time; Training; Upper arm; Vision; Visual; age related; aged; cell motility; critical period; dark rearing; early experience; end of life; experience; oculomotor; orbit muscle; postnatal; programs; protein complex; public health relevance; research study; respiratory; response; visual deprivation

DESCRIPTION (provided by applicant): The ocular motor system is arguably the best understood mammalian motor system. However, the extraocular muscles, its effector arms, remain somewhat of a black box. From a peculiar phenotype and extreme functional profile, to a disparate response to some neuromuscular disorders, these small muscles deviate from the skeletal muscle stereotype. Our results have demonstrated that the extraocular muscles have alternative arrangements for metabolic pathways considered vital for other skeletal muscles. Moreover, our pilot studies suggest that their mitochondria have unique properties as well, a fact that may explain their susceptibility to some mitochondrial myopathies. In this project, we will test the hypothesis that mitochondria are functionally different in the extraocular muscles and their content and properties are determined by visual experience and altered by aging. We will combine well-established functional and biochemical assays with models of visual deprivation and aging to achieve the following aims: (1) determine the factors that limit mitochondrial function in the extraocular muscles; (2) test whether extraocular muscle mitochondrial content and function are influenced by postnatal visual experience; and (3) determine how aging alters mitochondrial content and function in the extraocular muscles. The results will address three important gaps in our understanding of the basic biology of the extraocular muscles: the functional properties of their mitochondria, the development of their metabolic properties in the postnatal period, and aging. Therefore, we expect that the new knowledge will be applicable to disorders of ocular motility in the young (strabismus) and the aged (mitochondrial myopathies). PUBLIC HEALTH RELEVANCE: This project will study how the mitochondria, the cellular energy factories of the cells, are different in the small muscles that move the eyes. It will also demonstrate how normal vision early in life is very important to allow the eye muscles to achieve their capacity to generate energy and sustain high activity levels. Finally, these studies will explore the deleterious consequences of aging on eye muscle function.

描述(申请人提供)：眼球运动系统可以说是最了解哺乳动物的运动系统。然而，眼外肌，即它的效应器手臂，在某种程度上仍然是一个黑匣子。从特殊的表型和极端的功能特征，到对某些神经肌肉疾病的不同反应，这些小肌肉偏离了骨骼肌的刻板印象。我们的结果表明，眼外肌对其他骨骼肌至关重要的代谢途径有不同的安排。此外，我们的初步研究表明，它们的线粒体也具有独特的特性，这一事实可能解释了它们对一些线粒体肌病的易感性。在这个项目中，我们将检验这样一个假设，即眼外肌中的线粒体在功能上是不同的，它们的内容和性质是由视觉经验决定的，并随着年龄的增长而改变。我们将结合成熟的功能和生化分析与视觉剥夺和衰老模型来实现以下目标：(1)确定限制眼外肌线粒体功能的因素；(2)测试眼外肌线粒体的内容和功能是否受到出生后视觉体验的影响；以及(3)确定衰老如何改变眼外肌中的线粒体内容和功能。这些结果将解决我们对眼外肌基本生物学理解中的三个重要空白：它们的线粒体的功能特性，它们在出生后阶段代谢特性的发展，以及衰老。因此，我们期望新的知识将适用于年轻人(斜视)和老年人(线粒体肌病)的眼球运动障碍。与公共健康相关：这个项目将研究线粒体，即细胞的细胞能量工厂，在移动眼睛的小肌肉中是如何不同的。它还将展示生命早期的正常视力对于眼肌实现产生能量和维持高活动水平的能力是多么重要。最后，这些研究将探索衰老对眼睛肌肉功能的有害后果。