Functional role of sarcomeric nonmuscle myosin IIB in extraocular muscle

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 liB) is present in the sarcomeric A band of putative tonic EOM fibers. Although small amounts of nmMyH liB 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 liB in a tissue and time-specific manner in order to test the following central hypothesis: the sarcomeric distribution of nmMyH liB 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) detennine whether normal visual experience early in life is necessary for the expression and sarcomeric localization of nmMyH liB in rodent EOMs, 2) define the role of nmMyH fiB on sarcomeric structure in rodent EOMs and 3) determine the influence of nmMyH fiB on the contractile fUnction of rodent EO Ms. These results will establish the role of nmMyH liB 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.