Structural Basis of Amblyopia and Strabismus

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DESCRIPTION (provided by applicant): The ultimate objective of this project is to understand the neural mechanisms responsible for visual loss caused by two diseases: amblyopia and strabismus. Together, these conditions affect about 2% of the children in the United States. Amblyopia develops when one eye is deprived of normal visual stimulation during early childhood. For example, a congenital cataract impairs vision by preventing the retina from receiving clearly focused images. Even after the cataract is removed, the visual acuity in the eye remains poor, because visual deprivation has caused abnormal wiring of synaptic connections and disruption of cellular activity in the brain. In normal monkeys the synaptic connections in the primary visual cortex serving each eye are organized into a system of parallel, alternating bands, called ocular dominance columns. In some forms of amblyopia, these columns shrink and their cells lose responsiveness to the deprived eye. In Specific Aim #1, a metabolic label, cytochrome oxidase (CO), will be used to how ocular dominance columns are organized in humans, by examining post-mortem specimens of visual cortex obtained from patients with a history of visual loss in one eye. Patterns of metabolic activity will also be studied in amblyopia and strabismus, and in normal subjects in area V2, the next cortical area devoted to visual processing. In Specific Aim #2, connections will be traced from ocular dominance columns to area V2 in the macaque. The hypothesis is that a loss of projections from cells in the deprived eye's ocular dominance columns to area V2 is unimportant factor in amblyopia, because it prevents the normal transfer of visual information to higher centers. In Specific Aim #3, the neural mechanisms responsible for visual suppression will be examined. In strabismus, children fail to maintain normal alignment of the eyes. They avoid double vision by suppressing the image from one eye. How this occurs will be studied in strabismic macaques by testing their visual function and ocular fixation preference. Dichoptic perimetry will be employed to map patterns of visual suppression in the visual fields. After these psychophysical tests are completed, recordings will be made from single cells in awake animals, as they switch fixation back and forth between each eye. The goal will be to determine how the firing rate of cells is modulated by visual suppression. Iso-oriented and cross-oriented gratings will be used to search for binocular facilitation and suppression, and to test whether these effects depend upon which eye is perceptually dominant. Finally, areas of regional suppression in the visual fields will be correlated with patterns of CO activity in the ocular dominance columns. The hypothesis is that metabolic activity will be reduced in the suppressed eye's columns. New insights from these experiments into the structural basis of amblyopia and strabismus may lead to improved methods of preventing and treating these diseases.