In primates normal visual perception depends upon positioning the eyes so that objects of interest activate the foveae of both eyes. This is achieved through an impressively precise calibration of eye muscle growth and neural commands, a process that depends upon early binocular visual experience. For at least 3% of children born in the United States this developmental process is unsuccessful, which leads to a chronic misalignment of the eyes referred to as strabismus. In addition to the motor impairments, the loss of binocular visual experience often leads to substantial impairments of visual function, such as amblyopia. Numerous oculomotor abnormalities have also been reported, including asymmetrical smooth pursuit gain, a lack of disparity vergence, and disconjugate saccades. Existing treatments are successful in some individuals but in others misalignment persists or reappears in the years following treatment. Recent studies have suggested that this problem may be attributable, in part, to different neurodevelopmental trajectories in normal and strabismic individuals. At present, however, very little is known about the specific abnormalities of oculomotor circuitry that may underlie the disorder. For example, virtually nothing is known about the neurophysiology of saccadic circuitry in strabismus. The long-term goal of the proposed experiments, therefore, is to identify the specific neurophysiological abnormalities that lead to disordered saccades and that maintain the eyes in a misaligned state. Our hypothesis is that disordered brainstem saccadic commands influence the static eye misalignment. To test this idea, we have developed an animal model of infantile strabismus in macaques. Previously published behavioral data have shown that these animals have visual and eye movement abnormalities that closely match those found in human children. We will use a combination of single unit recording and microstimulation of brainstem oculomotor structures while monkeys perform saccade tasks. These studies would significantly advance our understanding of the neurological abnormalities that currently impede the development of improved treatments for infantile strabismus.

Public Health Relevance

Strabismus is a common disorder of eye alignment that can lead to significant abnormalities of visual function, including amblyopia and impaired stereoscopic depth perception. Our studies are designed to identify abnormalities of neural circuitry in strabismus with the goal of improving diagnosis and treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024248-04
Application #
9402621
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Araj, Houmam H
Project Start
2015-01-01
Project End
2019-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Washington
Department
Veterinary Sciences
Type
Primate Centers
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Walton, Mark M G; Mustari, Michael J (2017) Comparison of three models of saccade disconjugacy in strabismus. J Neurophysiol 118:3175-3193
Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome et al. (2017) Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome. J Neurophysiol 118:280-299
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) Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates. Invest Ophthalmol Vis Sci 56:3467-83
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
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