Temporal and Spatial Patterns of Structural Proteins in Extraocular Muscles

Grants and Contracts Details


Extraocular muscles (EOM), although classified as skeletal muscle, are unique in their developmental origin, developmental pattern of myosin heavy chain (MyHC) protein isoform expression and patterns of innervation. Interestingly, EOM are spared in many of the devastating muscular dystrophies that affect the peripheral skeletal muscle, such as Duchenne's and limb girdle muscular dystrophies and on the other hand are specifically targeted in oculopharyngeal muscular dystrophy and myasthenia gravis. The hypothesis driVing this proposal is that the unique nature of the myogenesis, myofibrillogenesis and maturation of the EOM provide the mechanisms for enhanced plasticity and regenerative properties. The EOM undergo a different developmental path than the somite derived skeletal muscles and therefore are affected by different signaling pathsways. Gene expression profiling of EOM have implicated the presence of both cardiac and skeletal muscle isoforms of myofibrillar and cytoskeletal mRNAs; however, with the notable exceptions of MyHC and myomesin, there is little biochemical data to substantiate these data. A major goal of this exploratory project as outlined in the specific aims is to evaluate the end products in these signaling pathways in the form of the cytoskeletal, myofibrillar and ECM proteins expressed in the developing and adult EOM and compare these protein distributions to prototypic fast muscle (both adult and developing) such as the EDL. We will use biochemical and immunological tools to examine the expression patterns of the myofibrillar, cytoskeletal and extracellular matrix of EOMs. This new information on the proteins that integrate the structural support and contractile elements of the developing and mature EOMs will yield insights into how this novel adult phenotype is established and should add to our understanding of how it is disrupted in strabismus.
Effective start/end date9/30/087/31/11


  • National Eye Institute: $402,875.00


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