The extraocular muscles (EOMs) are categorized as skeletal muscles;however, emerging evidence indicates that they deviate significantly from the prototypical members of this muscle class. For example, many myofilament, cytoskeletal and extracellular matrix proteins have unique expression patterns in developing and adult EOMs, including the sustained expression of embryonic and fetal myosin isoforms (MyHC), the presence of a unique EOM-specific MyHC, and co-expression of cardiac and skeletal muscle isoforms of thick and thin filament accessory proteins. We demonstrated that a nonmuscle myosin (nmMyH IIB) is present in the sarcomeric A band of putative tonic EOM fibers. Although small amounts of nmMyH IIB are found in the Z-line of cardiac and skeletal muscles, its unique distribution within the A band in EOM tonic fibers is further evidence of the complexity and unconventional developmental program of the eye muscles. We will use genetically engineered mice to delete nmMyH IIB in a tissue and time-specific manner in order to test the following central hypothesis: the sarcomeric distribution of nmMyH IIB in EOM fibers depends on normal visual experience postnatally and is necessary for normal EOM contractile function in the adult. Thus we have defined the following specific aims: 1) determine whether normal visual experience early in life is necessary for the expression and sarcomeric localization of nmMyH IIB in rodent EOMs, 2) define the role of nmMyH IIB on sarcomeric structure in rodent EOMs and 3) determine the influence of nmMyH IIB on the contractile function of rodent EOMs. These results will establish the role of nmMyH IIB in EOM fibers during early postnatal development and in the adult and should provide valuable insights into our understanding of the normal EOM phenotype and how it might change with disease.)

Public Health Relevance

In addition to the sensory pathways, the ability to direct the eyes to items of interest is also key for normal vision. The extraocular muscles are the small muscles responsible for coordinated eye movements. This project will examine the function of a structural protein found in a unique position only in the extraocular muscles and that may be important for normal eye movements.)

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021231-03
Application #
8512730
Study Section
Skeletal Muscle and Exercise Physiology Study Section (SMEP)
Program Officer
Araj, Houmam H
Project Start
2011-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$317,419
Indirect Cost
$103,669
Name
University of Kentucky
Department
Biochemistry
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Moncman, Carole L; Andrade, Miguel E; McCool, Andrea A et al. (2013) Development transitions of thin filament proteins in rat extraocular muscles. Exp Cell Res 319:23-31