Amblyopia is defined as a disease caused by abnormal visual experience during early childhood, which results in a decrease in acuity that can not be explained by pathology within the eye itself. For example, if a child is born with a dense cataract in one eye, the retina will be deprived of normal visual stimulation (Fig. 13). When the child grows up, the visual acuity in the affected eye will be poor -- even if the cataract is removed later by surgery and replaced by a clear lens of the appropriate refractive power. Without an ocular explanation for the permanent loss of vision caused by visual deprivation, investigators have long suspected that amblyopia is caused by anomalous wiring of the eye's central connections in the brain. This view has been confirmed by experiments suturing closed the lids of one eye in kittens or monkeys at an early age to simulate cataract (Wiesel and Hubel 1963, 1965; von Noorden et al. 1970). It is important to note that amblyopia develops only in the young, when the visual system is still immature, and hence vulnerable to the effects of deleterious environmental manipulations. This brief interval of early vulnerability is called the “critical period”.

Fig. 13) A child with amblyopia in the left eye due to a congenital cataract. Prolonged deprivation from the cataract can cause rewiring of connections in the visual cortex, leading to permanent visual loss despite later removal of the cataract.

      In primates, inputs to the primary visual cortex driven by the eyes are segregated in layer 4c into alternating bands of input known as ocular dominance columns. To determine if the ocular dominance columns require visual experience to develop, we examined striate cortex in newborn monkeys delivered by Caesarean section. We found that columns were present, although they were not quite as well segregated as in adults (Fig. 14):

Fig. 14) Autoradiographic montage of layer 4c in a macaque monkey at birth, showing ocular dominance columns arranged in an adult-like pattern. (From: Horton JC, Hocking DR. J. Neuroscience, 1996.)

      These studies indicate that formation of ocular dominance columns is programmed innately and not contingent on visual experience. The same is true for the cytochrome oxidase patches in V1 and the stripes in V2. From the location of the blind spot representation and the border of the monocular crescent in the cortex shown in Figure 14, one can also infer that the retinotopic map develops without visual experience.

      Although the ocular dominance columns do not require visual experience for their formation, they can be altered drastically by post-natal visual deprivation occurring during the critical period. In their classic studies, Hubel and Wiesel showed that visual deprivation causes shrinkage of the eye’s ocular dominance columns in the cortex. This phenomenon is presumed to contribute to the occurrence of amblyopia. Shrinkage of the ocular dominance columns reflects a loss of input from laminae of the lateral geniculate body conveying information from the deprived eye. This loss of input means that fewer cells are available in the cortex to handle information emanating from the deprived eye.

      We have shown in monkeys that shrinkage of ocular dominance columns is most severe when deprivation begins right after birth (Fig. 15):

Fig. 15) Autoradiographic montage (left) and drawing (right) of ocular dominance columns in layer 4c after deprivation of a macaque starting at age 1 week. The proline label was injected into the normal eye; the ocular dominance columns of the deprived eye appear as unlabeled, shrunken fragments of columns.

      These studies indicate that formation of ocular dominance columns is programmed innately and not contingent on visual experience. The same is true for the cytochrome oxidase patches in V1 and the stripes in V2. From the location of the blind spot representation and the border of the monocular crescent in the cortex shown in Figure 14, one can also infer that the retinotopic map develops without visual experience.

      Although the ocular dominance columns do not require visual experience for their formation, they can be altered drastically by post-natal visual deprivation occurring during the critical period. In their classic studies, Hubel and Wiesel showed that visual deprivation causes shrinkage of the eye’s ocular dominance columns in the cortex. This phenomenon is presumed to contribute to the occurrence of amblyopia. Shrinkage of the ocular dominance columns reflects a loss of input from laminae of the lateral geniculate body conveying information from the deprived eye. This loss of input means that fewer cells are available in the cortex to handle information emanating from the deprived eye.

      We have shown in monkeys that shrinkage of ocular dominance columns is most severe when deprivation begins right after birth (Fig. 15):

Fig. 16) Autoradiographic montage and drawing of the columns in a macaque deprived starting at age 5 weeks. The columns serving the deprived eye are much less shrunken, compared with deprivation commencing at age 1 week, as shown above. From: Horton JC, Hocking DR. J. Neuroscience, 1997.

      Shrinkage of ocular dominance columns means that connections serving the amblyopic eye are lost in the primary visual cortex. Cells in the primary visual cortex project heavily to the next visual area, V2. We inquired whether V1 to V2 projections are also affected in amblyopia (Fig. 17). Three animals were raised with monocular suture. [3H]proline was injected into one eye to label the ocular dominance columns. Cholera toxin B-gold (CTB-Au) was injected in V2 to label V1 projection neurons. Despite column shrinkage, cells in deprived and normal columns were equal in size and density, in both layer 2/3 and 4B. These data indicate that early monocular form deprivation does not alter the segregation of patch and interpatch pathways to V2 stripes, or cause selective loss or atrophy of V1 projection neurons. The effect of shrinkage of geniculocortical afferents in layer 4C following visual deprivation is not amplified further by attenuation of the amblyopic eye’s projections from V1 to V2. For further details, see: Sincich LC, Jockson CM, Horton JC. J. Neuroscience, 2012

Fig. 17) Projections from V1 to V2 in amblyopia. Visual deprivation of the right eye causes shrinkage of ocular dominance columns and reduction in the size of CO patches. Although the CO patches are smaller, they occupy a greater percentage of the deprived eye’s columns. The appearance of the thin, pale, and thick stripes in V2 remains normal in amblyopia. The density of projections from the deprived eye’s columns to V2 is not affected by amblyopia.