Determinants of extraocular muscle function

描述（由申请人提供）：眼运动系统可以说是最好理解的哺乳动物运动系统。然而，眼外肌，它的效应臂，仍然是一个黑匣子。从一个特殊的表型和极端的功能概况，以不同的反应，一些神经肌肉疾病，这些小肌肉偏离骨骼肌刻板印象。我们的研究结果表明，眼外肌的代谢途径被认为是至关重要的其他骨骼肌的替代安排。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某些线粒体肌病的易感性。在这个项目中，我们将测试线粒体在眼外肌中功能不同的假设，它们的内容和性质由视觉经验决定，并随着年龄的增长而改变。我们将结合联合收割机完善的功能和生物化学检测与视觉剥夺和衰老模型，以实现以下目标：（1）确定限制眼外肌线粒体功能的因素;（2）测试眼外肌线粒体含量和功能是否受出生后视觉体验的影响;（3）确定衰老如何改变眼外肌线粒体含量和功能。这些结果将解决我们对眼外肌基本生物学的理解中的三个重要空白：线粒体的功能特性，出生后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。 公共卫生相关性：这个项目将研究线粒体，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。它还将证明生命早期的正常视力对于允许眼部肌肉实现其产生能量和维持高活动水平的能力是非常重要的。最后，这些研究将探讨衰老对眼肌功能的有害影响。

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.