Brainstem saccade circuitry in strabismus

University Of Washington, Seattle WA

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Abstract

DESCRIPTION (provided by applicant): 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.