Alterations in visual experience during a well-defined postnatal window, the critical period, produce irreversible damage to vision. Knowledge of this critical period concept has dramatically improved how the pediatric ophthalmologist manages disorders of vision, eye alignment, and ocular motility. Taking a page from the visual critical period literature, the properties of the developing visuomotor system may be determinants of the cell and molecular diversity of extraocular muscle. The correlate of this hypothesis is that alterations in visuomotor development produce irreversible changes in extraocular muscle biology. Compelling evidence has emerged demonstrating that there is a critical period in the course of extraocular muscle development. Perturbations in visual development alter the expression of a myosin heavy chain gene that is uniquely expressed in extraocular muscle, while similar perturbations in the adult have no effect. Muscle is an elegant structure-function model, with coordinate regulation of traits that determine fiber type. The major tenet evolving from previous studies is that the developing visuomotor system exerts global effects on eye muscle development in the same way that visual experience globally influences visual function. Studies for the next project period are designed to develop an integrated concept of the extraocular muscle critical period.
Specific Aim 1 characterizes myosin gene regulation in relationship to the extraocular muscle critical period, using competitive PCR and mRNA cellular localization techniques.
Specific Aim 2 assesses the role that visuomotor development and the extraocular muscle critical period play in the maturation of mechanisms for calcium homeostasis and energy metabolism, by means of a battery of biochemical assays for rate-limiting enzymes.
Specific Aim 3 evaluates the nascent concept of an extraocular muscle critical period in subhuman primates. Extraocular muscle biology will be assessed in order to determine the consequences that altered visual development and congenital strabismus have for extraocular muscle of a foveate organism. Ultimately, the management of strabismus, not yet a perfect science, likely will be improved, as the relationship between the visual critical period and EOM development is better understood.
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