!"#$%!&$''' ' 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
Walton, Mark M G; Ono, Seiji; Mustari, Michael (2014) Vertical and oblique saccade disconjugacy in strabismus. Invest Ophthalmol Vis Sci 55:275-90
Walton, Mark M G; Ono, Seiji; Mustari, Michael J (2013) Stimulation of pontine reticular formation in monkeys with strabismus. Invest Ophthalmol Vis Sci 54:7125-36
Ono, Seiji; Das, Vallabh E; Mustari, Michael J (2012) Conjugate adaptation of smooth pursuit during monocular viewing in strabismic monkeys with exotropia. Invest Ophthalmol Vis Sci 53:2038-45
Brostek, Lukas; Eggert, Thomas; Ono, Seiji et al. (2011) An information-theoretic approach for evaluating probabilistic tuning functions of single neurons. Front Comput Neurosci 5:15
Mustari, Michael J; Ono, Seiji (2011) Neural mechanisms for smooth pursuit in strabismus. Ann N Y Acad Sci 1233:187-93
Ono, Seiji; Mustari, Michael J (2010) Visual error signals from the pretectal nucleus of the optic tract guide motor learning for smooth pursuit. J Neurophysiol 103:2889-99
Mustari, Michael J; Ono, Seiji; Das, Vallabh E (2009) Signal processing and distribution in cortical-brainstem pathways for smooth pursuit eye movements. Ann N Y Acad Sci 1164:147-54
Crowder, Nathan A; Price, Nicholas S C; Mustari, Michael J et al. (2009) Direction and contrast tuning of macaque MSTd neurons during saccades. J Neurophysiol 101:3100-7
Ibbotson, Michael R; Crowder, Nathan A; Cloherty, Shaun L et al. (2008) Saccadic modulation of neural responses: possible roles in saccadic suppression, enhancement, and time compression. J Neurosci 28:10952-60
Cheng, Georgiana; Kaminski, Henry J; Gong, Bendi et al. (2008) Monocular visual deprivation in macaque monkeys: a profile in the gene expression of lateral geniculate nucleus by laser capture microdissection. Mol Vis 14:1401-13

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