Approximately 1-2% of the American population suffer visual loss from amblyopia, despite improved standards of detection and treatment. Over the past quarter century, extensive scientific investigations performed in cats and monkeys have helped to elucidate the anatomical and physiological basis of amblyopia. However, little no direct information is available about the pathological changes that occur in the human visual cortex in amblyopia, in part because most of the experimental techniques developed for animal studies cannot be used in man. Cytochrome oxidase histochemistry was introduced by Wong-Riley in 1978 for mapping metabolic activity in the brain. This method has the special advantage that it can be applied to study patterns of metabolic activity in human post-mortem specimens. We have previously used the technique to reveal for the first time the arrangement of the ocular dominance columns in adult human visual cortex. We now propose to apply the cytochrome oxidase method to specimens of visual cortex obtained post-mortem from patients with a history of early visual loss. By examining a series of human cases involving actual loss of one eye (e.g. retinoblastoma, trauma) at various ages, it will be possible to determine the period of """"""""plasticity"""""""" for the ocular dominance columns in humans. Cases from patients with a history of unilateral media opacity (e.g. cataract), strabismus, or anisometropia will provide new information about the anatomical and metabolic changes which occur in visual cortex from amblyopia. To interpret human autopsy studies reliably, it is important to conduct correlative experiments in animals, comparing patterns of cytochrome oxidase activity with other anatomical techniques. Despite the cost involved, the macaque monkey is the most appropriate species, because it has highly organized, well defined ocular dominance columns that appear extremely similar by cytochrome oxidase histochemistry to those in the human visual cortex. At one week of age, 2 monkeys will undergo monocular enucleation and 4 monkeys will undergo monocular eyelid suture. Six months later, the animals will receive anterograde tracer injections into single lamina of the lateral geniculate body to label the ocular dominance columns. Cytochrome oxidase activity will then be correlated with the labeled ocular dominance columns. These animal experiments will provide information essential for interpreting our parallel studies in human autopsy cases.
| Horton, J C; Stryker, M P (1993) Amblyopia induced by anisometropia without shrinkage of ocular dominance columns in human striate cortex. Proc Natl Acad Sci U S A 90:5494-8 |
