!"#$%!&$''' ' 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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY006069-28
Application #
8628676
Study Section
Special Emphasis Panel (SPC)
Program Officer
Araj, Houmam H
Project Start
1990-09-30
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
28
Fiscal Year
2014
Total Cost
$393,480
Indirect Cost
$168,480
Name
University of Washington
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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
Brostek, Lukas; Büttner, Ulrich; Mustari, Michael J et al. (2015) Eye Velocity Gain Fields in MSTd During Optokinetic Stimulation. Cereb Cortex 25:2181-90
Walton, Mark M G; Mustari, Michael J (2015) Abnormal tuning of saccade-related cells in pontine reticular formation of strabismic monkeys. J Neurophysiol 114:857-68
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
Cloherty, Shaun L; Crowder, Nathan A; Mustari, Michael J et al. (2015) Saccade-induced image motion cannot account for post-saccadic enhancement of visual processing in primate MST. Front Syst Neurosci 9:122
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
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
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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