Binocular vision is such a natural experience that we take it for granted. The stream of images from each eye is fused within the brain to create a single view of the world. Within weeks of birth, infants learn to align and move their eyes together, so that targets are projected accurately onto each retina. Once the eyes become aligned, binocular depth perception begins to emerge. Unfortunately, in 2% of children, ocular alignment fails, giving rise to strabismus. When the eyes become misaligned in adults, the result is double vision or diplopia. When strabismus develops in children, diplopia also occurs, but only transiently. Within days, children suppress one image. This sensory adaptation is helpful, because it eliminates diplopia. However, it is also harmful, because it deprives the visual system of the feedback required to maintain ocular alignment. Instead of adjusting the eye muscles to re-align the globes, children tolerate strabismus. The deviated eye often develops amblyopia, or lazy eye, because of chronic suppression. A major goal of this research project is to learn how suppression occurs in the brain. Recently, we have performed dichoptic visual field mapping in human patients to define the pattern of visual suppression that occurs in exotropia, or outwards eye deviation. We have also raised monkeys with exotropia, by weakening the medial rectus eye muscles after birth. These animals display patterns of visual suppression nearly identical to those in humans. To have a macaque model of strabismus is valuable, because it is possible to record the electrical discharges of single neurons to define the basic neural mechanism of suppression.
In Specific Aim #1, we will record from the primary visual cortex of macaques with strabismus, in whom suppression scotomas have been previously mapped, to compare the responses of single units during monocular versus binocular stimulation. The hypothesis is that cells with receptive fields located within an eye's suppression scotoma may respond to monocular stimulation, but will be inhibited when the other, dominant eye is also stimulated.
In Specific Aim #2, we will examine how human subjects with strabismus decide which eye to use to look at targets in their visual environment. After mapping of suppression scotomas, subjects will be presented with peripheral targets visible to only the right eye, the left eye, or potentialy either eye. For each location in the visual field, we will determine if the eye that acquired the target was the eye that perceived the target. This experiment will reveal whether people with strabismus sometimes use one eye to acquire target location, and the other eye to saccade to it.
In Specific Aim #3, we will investigate the topography and properties of cells in the superior colliculus, a brainstem center that controls eye movements, to probe the neural mechanisms governing eye selection for saccades in primates with strabismus. Knowledge gained from this work may provide a new basis for developing strategies to prevent and treat strabismus.

Public Health Relevance

Deviation of the eyes, a condition called strabismus, is a common visual problem that affects the ocular health of children and adults in the United States. Development of better treatments has been hampered by limited understanding - at a fundamental level - of the sensory and motor adaptations that occur in this disease. Information gained from this research proposal about the neural mechanism of suppression, the localization of visual targets, and the control of eye movements may help people with strabismus.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010217-24
Application #
9398120
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Araj, Houmam H
Project Start
1993-07-01
Project End
2018-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
24
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Horton, Jonathan C; Fahle, Manfred; Mulder, Theo et al. (2017) Adaptation, perceptual learning, and plasticity of brain functions. Graefes Arch Clin Exp Ophthalmol 255:435-447
Horton, Jonathan C; Barkovich, A James (2017) Bilateral Optic Disc Pits With Posterior Pituitary Ectopia. J Neuroophthalmol 37:401-402
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2017) Capturing the Moment of Fusion Loss in Intermittent Exotropia. Ophthalmology 124:496-504
Adams, Daniel L; Economides, John R; Horton, Jonathan C (2017) Incomitance and Eye Dominance in Intermittent Exotropia. Invest Ophthalmol Vis Sci 58:4049-4055
Horton, Jonathan C (2017) Invited Commentary: Ganglion Cell Complex Measurement in Compressive Optic Neuropathy. J Neuroophthalmol 37:13-15
Adams, Daniel L; Economides, John R; Horton, Jonathan C (2016) Cortical Representation of a Myopic Peripapillary Crescent. Ophthalmology 123:1494-9
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2016) Variability of Ocular Deviation in Strabismus. JAMA Ophthalmol 134:63-9
Han, Seunggu J; Magill, Stephen T; Tarapore, Phiroz E et al. (2016) Direct visualization of improved optic nerve pial vascular supply following tuberculum meningioma resection: case report. J Neurosurg 125:565-9
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2016) Normal correspondence of tectal maps for saccadic eye movements in strabismus. J Neurophysiol 116:2541-2549
Guterman, Elan L; Botelho, James V; Horton, Jonathan C (2016) Diagnosis of Tensilon-Negative Ocular Myasthenia Gravis By Daily Selfie. J Neuroophthalmol 36:292-3

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