Strabismus is a disease that develops in 1-2% of children, affecting many for the rest of their lives. It is characterized by misalignment of the eyes. The crucial point is that the ocular misalignment usually occurs without any abnormality of the cranial nerves or intrinsic disorder of the eyes. The primary culprit is a failure of the neural mechanisms responsible for maintaining binocular fusion. The goal of this project is to elucidate the defects in brain function responsible for strabismus. Children with strabismus avoid seeing two images by using visual suppression, at the cost of stereovision. If the suppression remains constant in one eye, rather than alternating between the eyes, they may also develop amblyopia. Visual suppression is a critical factor in the development of strabismus, because it eliminates the drive to compensate by fusing separate images. It is unknown how visual suppression occurs, or even where signals from the deviated eye are blocked in the visual pathway. The first specific aim in this grant is to map the visual fields in a large population of human subjects with common forms of strabismus: infantile esotropia, accommodative esotropia, and exotropia. The testing will be done under dichoptic conditions, by presenting different colored images to each eye of subjects wearing colored filters. These experiments will reveal which portions of the visual field are perceived by each eye. The second specific aim is to map dichoptic visual fields in macaques raised with strabismus. The macaque is extremely similar to the human in the organization and function of its visual system.
This aim will determine if macaques with strabismus exhibit suppression scotomas similar to those in humans. The advantage of pursuing experiments in nonhuman primates is that one can perform microelectrode studies in the visual cortex to probe the neural basis of visual suppression. The third specific aim is to undertake electrophysiological recordings in awake, strabismic macaques while they are looking with both eyes at visual stimuli, to learn how binocular interactions at the level of single cells give rise to suppression scotomas. Recordings will be made in different regions of the primary visual cortex (V1) in both hemispheres, to correlate single cell recordings with previously mapped suppression scotomas. The fourth specific aim is to examine the pattern of metabolic activity in V1 of macaques with strabismus. Inputs serving each eye are organized into alternating bands called ocular dominance columns. Strabismus induces abnormal staining patterns of the mitochondrial enzyme, cytochrome oxidase (CO), in ocular dominance columns. The pattern of CO activity throughout each V1 will be documented and compared with the pattern of suppression in the visual field mapped behaviorally. If there is a match, it will establish that suppression is mediated by a reduction of activity in columns of cells serving the non-perceiving eye within a suppression scotoma.

Public Health Relevance

This project will determine how children with strabismus avoid double vision by suppressing signals emanating from local regions of the retina in each eye. Elucidating the mechanism of visual suppression may lead to better methods to prevent and treat strabismus.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Araj, Houmam H
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Adams, Daniel L; Rapone, Brittany C; Economides, John R et al. (2018) Spontaneous Reattachment of the Medial Rectus After Free Tenotomy. J Pediatr Ophthalmol Strabismus 55:335-338
Economides, John R; Rapone, Brittany C; Adams, Daniel L et al. (2018) Normal Topography and Binocularity of the Superior Colliculus in Strabismus. J Neurosci 38:173-182
Horton, Jonathan C; Barkovich, A James (2017) Bilateral Optic Disc Pits With Posterior Pituitary Ectopia. J Neuroophthalmol 37:401-402
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
Adams, Daniel L; Economides, John R; Horton, Jonathan C (2017) Incomitance and Eye Dominance in Intermittent Exotropia. Invest Ophthalmol Vis Sci 58:4049-4055
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2017) Capturing the Moment of Fusion Loss in Intermittent Exotropia. Ophthalmology 124:496-504
Horton, Jonathan C (2017) Invited Commentary: Ganglion Cell Complex Measurement in Compressive Optic Neuropathy. J Neuroophthalmol 37:13-15
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
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

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