!""""""""#$%!&$''' ' Primates make extensive use of binocular, frontal vision in their daily behavior. Much of our visual function is dedicated to central (foveal) vision where retinal ganglion cell densities and the associated cortical magnification factor are highest. To examine an object in detail its image must be kept relatively stable on or near the fovea. This is accomplished by foveating (e.g., smooth pursuit and saccades) and stabilizing (e.g., optokinetic and vestibular ocular) eye movement systems. The visual and oculomotor systems of human and non-human primates are immature at birth and sensitive to injury. At least 3% of children born in the United States have compromised visual and eye movement function leading to misalignment of the eyes (strabismus), impaired gaze-holding (nystagmus), disorders of eye movements (smooth pursuit asymmetry, dysconjugacy) and amblyopia. The long-term goal of this project is to determine neural mechanisms that could be causal for these disorders. Our overarching hypothesis is that specific regions of the frontal and parietal cortex and their brainstem targets contribute differentially to defective eye movements, gaze-holding, eye misalignment, and impaired visual function. To address these problems, we have developed macaque models for infantile strabismus, which have virtually the same syndrome components as those observed in children with developmental strabismus. We use single unit recording during smooth pursuit and other tracking behaviors to determine how neural circuits are altered in developmental strabismus. The significance of our work is that different developmental or disease processes lead to permanent loss of visual-oculomotor function across the lifespan. Yet we know relatively little about how neural circuits are compromised in developmental disorders like strabismus and amblyopia. Therefore, our studies are designed to test real neural circuits in a manner that will aid in the diagnosis, treatment and cure of disorders associated with strabismus, neurodegenerative disease and brain injury. ! ''

Public Health Relevance

Developmental disorders such as strabismus can lead to loss of eye movement function and degraded vision or amblyopia. Our studies are designed to advance our understanding of how neural circuits are changed in developmental or strabismus in order to improve diagnosis, treatment and develop cures for disabling visual-motor disorders across the lifespan.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (SPC)
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Araj, Houmam H
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University of Washington
Schools of Medicine
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Bakst, Leah; Fleuriet, Jérome; Mustari, Michael J (2017) FEFsem neuronal response during combined volitional and reflexive pursuit. J Vis 17:13
McMillan, A; Mustari, M; Horn, A (2017) Identification of secondary vestibulo-ocular neurons in human based on their histochemical characteristics found in monkey. J Neurol 264:583-585
Walton, Mark M G; Mustari, Michael J (2017) Comparison of three models of saccade disconjugacy in strabismus. J Neurophysiol 118:3175-3193
Ono, Seiji; Mustari, Michael J (2016) Response properties of MST parafoveal neurons during smooth pursuit adaptation. J Neurophysiol 116:210-7
McLoon, Linda K; Christiansen, Stephen P; Ghose, Geoffrey M et al. (2016) Improvement of Eye Alignment in Adult Strabismic Monkeys by Sustained IGF-1 Treatment. Invest Ophthalmol Vis Sci 57:6070-6078
Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji et al. (2016) Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys. Invest Ophthalmol Vis Sci 57:3168-80
Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M et al. (2015) Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment. Invest Ophthalmol Vis Sci 56:3484-96
Walton, Mark M G; Mustari, Michael J; Willoughby, Christy L et al. (2015) Abnormal activity of neurons in abducens nucleus of strabismic monkeys. Invest Ophthalmol Vis Sci 56:10-9
Tang, Xiaofang; Büttner-Ennever, Jean A; Mustari, Michael J et al. (2015) Internal organization of medial rectus and inferior rectus muscle neurons in the C group of the oculomotor nucleus in monkey. J Comp Neurol 523:1809-23
Willoughby, Christy L; Fleuriet, Jérome; Walton, Mark M et al. (2015) Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates. Invest Ophthalmol Vis Sci 56:3467-83

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