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 macaque monkeys who have infantile visual cortex that provide mechanisms for the behaviors. The specific goal of the proposed research is to determine if eye realignment early in the critical period can repair these behavioral and structural deficits. The following hypothesis will be tested in each animal: Hypothesis 1: Macaques who have infantile strabismus have maldeveloped pursuit eye movements that can be repaired by early realignment of the eyes; the earlier the realignment, the greater the ocular motor recovery. Newborn macaques will be reared wearing prism-goggles to cause optical strabismus. The strabismus will be repaired by removing the prisms at one of three postnatal ages (3 weeks, e months, or 6 months), corresponding to """"""""very early"""""""" (3 months), """"""""average"""""""" ( 12 months), and """"""""late"""""""" (2 years) strabismus surgery in human infants. After several months of eye realignment, pursuit will be recorded in each macaque. If pursuit is more normal in monkeys realigned at earlier ages, earlier realignment will be considered to be effective for repairing ocular motor circuits. Hypothesis 2: Strabismic macaques have abnormalities of random-dot stereogram VEP function and motion VEP function that can be repaired by early realignment of the eyes; the earlier the realignment, the greater the electrophysiological recovery. Binocular stereogram VEPs and monocular motion VEPs will be recorded in strabismic monkeys whose eyes are realigned at the postnatal ages designated under Hypothesis 1. If the VEP responses are improved in animals realigned at earlier ages, early realignment will be considered to be effective for repairing cortical circuits that mediate stereopsis and motion sensitivity. Hypothesis 3: Strabismic macaques have structural abnormalities in visual cortex that: a) correlate with their pursuit eye movement and VEP behavioral """"""""indicators"""""""", and b) can be repaired by early realignment of the eyes; the earlier the realignment, the greater the neuroanatomic recovery. In striate cortex (area V 1) of macaques with untreated strabismus, horizontal connections between ocular dominance columns (ODCs) tend to skip opposite-eye columns and join same-eye columns. The defect occurs in V1 layers known to be important for pursuit/motion processing and stereopsis/fusion. ODCs in each animal will be infected using beads to label binocularly-connected neurons. If the number of binocularly-labeled neurons increases in animals realigned at earlier ages, early realignment will be considered to be effective for repairing binocular cortical circuits that mediate pursuit, motion sensitivity and stereopsis. The experiments proposed here could lead to refined treatments aimed at achieving functional cures, as well as a fundamental advance in understanding the biological mechanism of a common pediatric visual disorder.
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