Determinants of extraocular muscle function

University Of Kentucky, Lexington KY

Investigators

Linked publications & trials

Abstract

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.