Strabismus is a common condition in children that frequently leads to permanent visual impairment. Available treatment options target the extraocular muscles when they are not fully developed. The extraocular muscles are different from other muscles;they even have their own tissue-specific myosin isoform, EOM-specific myosin, which appears soon after birth during a period of postnatal extraocular muscle development linked to visual experience: absence of vision during this time disrupts EOM-specific myosin expression and alters the contractile properties of the extraocular muscles, perhaps permanently. The same changes occur in strabismus patients, and may explain the need for multiple surgeries to restore normal eye position in many of them. This project will answer two questions: to what extent EOM-specific myosin defines normal extraocular muscle function, and how eye muscle function changes when the expression of this tissue-specific myosin is altered. To address these issues, we will ablate or restore the EOM-specific myosin gene to test the relevance of this myosin isoform to extraocular muscle function and integrity. The experimental approach relies on our recently developed mouse strains that permit control of the expression of the EOM-specific myosin gene, and will test the hypothesis that EOM-specific myosin is necessary for normal development of extraocular muscle structure and function, and its appearance after its normal postnatal window does not restore muscle function.
Specific Aim 2 will determine the consequences of EOM-specific myosin gene ablation on the postnatal development of mouse extraocular muscle structure and function.
Specific Aim 2 will test whether the recovery of EOM-specific myosin expression in the adult mouse restores extraocular muscle function. The answers that will result from the completion of this project will inform the timing of surgical and medical treatment for congenital strabismus.

Public Health Relevance

The extraocular muscles are the small muscles that move the eyes to keep them on the visual target of interest;one of their defining characteristics is tht they have a unique form of myosin, EOM-specific myosin, a special protein that influences how these muscles work. This protein is lost in patients with strabismus (crossed eyes). This project will determine what happens to eye muscle function when this protein is absent. The results from these studies will be important for our understanding of extraocular muscle function, and how it is affected in congenital and acquired strabismus.

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Skeletal Muscle Biology and Exercise Physiology Study Section (SMEP)
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Araj, Houmam H
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University of Kentucky
Schools of Medicine
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Stahl, John S; Thumser, Zachary C; May, Paul J et al. (2015) Mechanics of mouse ocular motor plant quantified by optogenetic techniques. J Neurophysiol 114:1455-67