The long-term goal of this research is to identify structural abnormalities in macaque visual cortex that help explain major sensorimotor deficits in infantile strabismus. The preliminary studies suggest that naturally-strabismic macaque is an appropriate model of the human disorder for three reasons: 1) the animals have a characteristic directional deficit of smooth pursuit, 2) the animals have deficits in binocular beat and motion VEPs; and 3) the animals have anatomic deficits in Vl binocular connectivity. The specific goal of this work is to study these behavioral and anatomic deficits in a larger group of naturally strabismic macaques. The following hypotheses will be tested in each animal: Hypothesis 1: Macaques who have onset of natural strabismus in infancy have a pursuit eye movement """"""""behavioral indicator"""""""" similar to that recorded in strabismic humans. Humans with infantile strabismus have a directional asymmetry of horizontal pursuit under conditions of monocular viewing. Pursuit acceleration for nasalward target motion in the visual field is consistently greater than pursuit acceleration for temporalward target motion. Pursuit will be recorded in the strabismic macaque and will be considered similar to human if there is a significant asymmetry of mean smooth eye acceleration favoring nasalward motion. Hypothesis 2: Naturally-strabismic macaques have abnormalities of binocular VEP function and motion VEP function similar to VEP """"""""indicators"""""""" recorded in strabismic humans. Strabismic humans have responses to binocular """"""""beat"""""""" VEPs that are significantly reduced in signal amplitude compared to normal human. Humans with infantile strabismus also have asymmetric motion VEPs; their VEP response for temporalward monocular motion is reduced compared to that for nasalward motion (analogous to the pursuit asymmetry). Binocular beat and motion VEPs will be recorded in the strabismic macaque and the VEP-indicators will be considered similar to strabismic human if the appropriate responses are significantly subnormal compared to normal macaque. Hypothesis 3: Naturally-strabismic macaques have structural abnormalities in visual cortex that correlate with their eye movement and VEP """"""""indicators"""""""". Following eye movement and VEP recording, striate cortex in each animal will be studied using neuroanatomic labeling techniques. WGA-HRP will be used to measure differences in width of ocular dominance columns; cytochrome oxidase will be used to reveal inequalities in metabolic activity of dominance columns; and biotinylated dextran amine will be used to reveal abnormal connectivity between dominance columns. Correlations will be sought between the magnitude of these structural abnormalities and the magnitude of the pursuit and VEP indicators.

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National Eye Institute (NEI)
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Visual Sciences B Study Section (VISB)
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Washington University
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Hoekel, James; Chisholm, Smith Ann; Al-Lozi, Amal et al. (2014) Ophthalmologic correlates of disease severity in children and adolescents with Wolfram syndrome. J AAPOS 18:461-465.e1
Ghasia, Fatema; Tychsen, Lawrence (2014) Horizontal and vertical optokinetic eye movements in macaque monkeys with infantile strabismus: directional bias and crosstalk. Invest Ophthalmol Vis Sci 55:265-74
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