STRUCTURAL BASIS OF AMBLYOPIA IN MONKEYS & HUMANS

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Significance Amblyopia (lazy eye) causes visual loss in 2% of the American population. Our research is directed at elucidating structural changes in the primate visual cortex which occur from visual deprivation. Objectives Visual deprivation induced by monocular eyelid suture, a laboratory model for congenital cataract, results in shrinkage of ocular dominance columns serving the closed eye. We performed monocular suture in macaques at ages 1,3,5,7, and 12 weeks to define the critical period for plasticity of ocular dominance columns. Results After a minimum survival of 8 months, complete montages of [3H]proline-labelled columns were reconstructed from flat-mounts of striate cortex in both hemispheres. Visual deprivation induced the columns throughout V1 to retract the same distance from their original borders in layer IVc(. At the earliest age we tested (1 week), visual deprivation reduced the columns to fragments. These fragments always coincided with a cytochrome oxidase patch, or a short string of patches, in the upper layers. More severe column shrinkage occurred in layer IVc( (parvo) than layer IVca (magno). The geniculate input to the patches in layer III (konio) appeared normal after deprivation, despite loss of CO activity. Surprisingly, the blind spot representation of the open eye was shrunken by monocular deprivation, although binocular competition is absent in this region. We found that eyelid suture at age 1 week caused the most severe column shrinkage. With suture at later ages, the degree of column shrinkage showed a progressive decline. This implies that primate visual cortex is most vulnerable to deprivation during the first weeks of life, and should provide further impetus for treatment of children with congenital cataract at the earliest possible age. Future Directions Analysis of the changes in connections between cortical layers which occur in amblyopia and initiation of new studies regarding the cortical basis of strabismus (crossed eyes). KEYWORDS ocular dominance column, critical period, amblyopia, visual deprivation, cytochrome oxidase patch, flat-mount, striate cortex, strabismus