The long-term goal of this research is to reveal the neural mechanisms that explain the behavioral deficits of infantile strabismus. The findings of our progress report indicate that infant monkeys with strabismus are an appropriate behavioral model of the human disorder, and have structural defects of visual cortex that help explain the behaviors. The specific goal of this research is to determine the age at which treatment of strabismus in macaques is capable of repairing these behavioral and structural deficits. The following hypotheses will be tested in each animal: Hypothesis 1. Macaques with strabismus-onset at birth have mal-developed pursuit eye movements that can be repaired if the strabismus is corrected by age about 6-9 weeks. Newborn macaques will be reared wearing prism-goggles to cause optical strabismus. The strabismus will be repaired by removing the prisms at one of four postnatal ages (3, 6, 9 or 12 wks), corresponding to """"""""early""""""""(3 mos human), """"""""early-intermediate""""""""(6 mos), """"""""delayed-intermediate"""""""" (9 mos) and """"""""delayed"""""""" (12 mos) strabismus surgery in human infants. Pursuit will then be recorded in each macaque. If pursuit is more normal in monkeys realigned at earlier ages, early realignment will be considered to be effective for repairing pursuit pathways. Hypothesis 2: Macaques with strabismus-onset 3 weeks after birth have mal-developed pursuit; the mal-development can be repaired if the duration of strabismus does not exceed 3 weeks. Optical strabismus will be induced after 3 wks (3 mos human) of normal visual experience, and will endure for 3, 6, 9 or 12 wks. After these intervals the strabismus will be repaired by prism removal and pursuit will be recorded. If pursuit is more normal in monkeys realigned after shorter durations of strabismus, prompt realignment will be considered to be effective for repairing pursuit. Hypothesis 3: Strabismic macaques have mal-developed short-latency ocular following and vergence eye movements that can be repaired if the strabismus is corrected within the time frames specified in Hypotheses 1 and 2. Ocular following and vergence eye movements will be recorded in monkeys with optical strabismus whose eyes are realigned at the post-natal ages designated under Hypotheses 1 and 2. If the amplitude and velocity of these movements are significantly greater in monkeys realigned at earlier ages/shorter durations, early/prompt realignment will be considered to be effective for repairing ocular following and short-latency vergence pathways. Hypothesis 4: Strabismic macaques have structural abnormalities in visual cortex that: a) correlate with their pursuit, ocular following and vergence behavioral """"""""indicators,"""""""" and b3 can be repaired by early realignment of the eyes; the earlier the realignment, the greater the neuroanatomic recovery. Ocular dominance columns (ODCs) of V1 will be labeled by transneuronal transport of [3H] proline, and BDA will be injected into ODCs to label binocular connections (horizontal projections). If the number of binocular connections increases in animals realigned at earlier ages/shorter durations, early/prompt realignment will be considered to be effective for repairing binocular cortical circuits that mediate pursuit, disparity vergence and ocular following. The experiments proposed here could lead to refined treatments and functional cures in humans, and reveal the biological mechanisms responsible for this common childhood visual disorder.
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