It has been shown that the visual acuity loss experienced by the deprived eye of kittens following an early period of monocular deprivation (MD) can be alleviated rapidly following 10 days of complete darkness when imposed even as late as 14 weeks of age. To examine whether 10 days of darkness conferred benefits at any age, we measured the extent of recovery of the visual acuity of the deprived eye following the darkness imposed on adult cats that had received the same early period of MD as used in prior experiments conducted on kittens. Parallel studies conducted on different animals examined the extent to which darkness changed the magnitude of the MD-induced laminar differences of the cell soma size and immunoreactivity for the neurofilament (NF) protein in the dorsal lateral geniculate nucleus (dLGN). The results indicated that 10 days of darkness imposed at one year of age neither alleviated the acuity loss of the deprived eye induced by an earlier period of MD nor did it decrease the concurrent lamina differences of the soma size or NF loss in the dLGN.

Over the last 35 years or so, there has been substantial progress in revealing and characterizing the many interesting and sometimes mysterious sensory abnormalities that accompany amblyopia. A goal of many of the studies has been to try to make the link between the sensory losses and the underlying neural losses, resulting in several hypotheses about the site, nature, and cause of amblyopia. This article reviews some of these hypotheses, and the assumptions that link the sensory losses to specific physiological alterations in the brain. Despite intensive study, it turns out to be quite difficult to make a simple linking hypothesis, at least at the level of single neurons, and the locus of the sensory loss remains elusive. It is now clear that the simplest notion—that reduced contrast sensitivity of neurons in cortical area V1 explains the reduction in contrast sensitivity—is too simplistic. Considerations of noise, noise correlations, pooling, and the weighting of information also play a critically important role in making perceptual decisions, and our current models of amblyopia do not adequately take these into account. Indeed, although the reduction of contrast sensitivity is generally considered to reflect “early” neural changes, it seems plausible that it reflects changes at many stages of visual processing.

Contrast-modulated (CM) stimuli are processed by spatial mechanisms that operate at larger spatial scales than those processing luminance-modulated (LM) stimuli and may be more prone to deficits in developing, amblyopic, and aging visual systems. Understanding neural mechanisms of contour interaction or crowding will help in detecting disorders of spatial vision. In this study, contour interaction effects on visual acuity for LM and CM C and bar stimuli are assessed in normal foveal vision. In Experiment 1, visual acuity is measured for all-LM and all-CM stimuli, at ∼3.5× above their respective modulation thresholds. In Experiment 2, visual acuity is measured for Cs and bars of different type (LM C with CM bars and vice versa). Visual acuity is degraded for CM compared with LM Cs (0.46 ± 0.04 logMAR vs. 0.18 ± 0.04 logMAR). With nearby bars, CM acuity is degraded further (0.23 ± 0.01 logMAR or ∼2 lines on an acuity chart), significantly more than LM acuity (0.11 ± 0.01 logMAR, ∼1 line). Contour interaction for CM stimuli extends over greater distances (arcmin) than it does for LM stimuli, but extents are similar with respect to acuities (∼3.5× the C gap width). Contour interaction is evident when the Cs and bars are defined differently: it is stronger when an LM C is flanked by CM bars (0.17 ± 0.03 logMAR) than when a CM C is flanked by LM bars (0.08 ± 0.02 logMAR). Our results suggest that contour interaction for foveally viewed acuity stimuli involves feature integration, such that the outputs of receptive fields representing Cs and bars are combined. Contour interaction operates at LM and CM representational stages, it can occur across stage, and it is enhanced at the CM stage. Greater contour interaction for CM Cs and bars could hold value for visual acuity testing and earlier diagnosis of conditions for which crowding is important, such as in amblyopia.

Unilateral eyelid suture, a model for amblyopia induced by congenital cataract, produces shrinkage of the deprived eye's ocular dominance columns in the striate cortex. Loss of geniculocortical projections are thought to account for the poor vision in the amblyopic eye. It is uncertain whether ocular dominance columns become shrunken in other forms of amblyopia. We examined the striate cortex in a pigtailed macaque with natural anisometropia discovered at age 5 months. Amblyopia in the left eye was documented at 1 year by behavioral testing. At age 6 years, the left eye was injected with [3H]proline and the striate cortex was processed for autoradiography and cytochrome oxidase (CO). The ocular dominance columns in layer IVc labelled with [3H]proline were normal. CO staining showed a novel pattern of thin dark bands in layer IV. These bands occupied the core zones at the center of the ocular dominance columns. Their appearance resulted from relative loss of CO activity along the borders of the ocular dominance columns, regions specialized for binocular processing. These findings indicate that not all forms of amblyopia are accompanied by shrinkage of ocular dominance columns. The unusual pattern of CO staining in layer IVc reflected a subtle alteration in metabolic activity which may have resulted from impairment of binocular function in anisometropic amblyopia.

Previous experiments in animals have shown that early unilateral eyelid suture, a model of amblyopia induced by cataract, causes shrinkage of ocular dominance columns serving the deprived eye in the striate cortex. It is unknown whether the ocular dominance columns are affected in amblyopia produced by strabismus. We examined specimens of striate cortex obtained postmortem from a 79-year-old woman with a history of amblyopia in her left eye (20/800) since age 2 from accommodative esotropia. Four years prior to her death, she suffered an ischemic infarct of the left optic disc. This injury to the left optic disc made it possible to label the ocular dominance columns using cytochrome oxidase histochemistry. The pattern of ocular dominance columns was reconstructed throughout most of the right striate cortex. No shrinkage of columns was found. In the left cortex only half the column mosaic was labelled, because the patient had some residual vision in the temporal retina of her left eye. The columns within the labelled portion of the overall mosaic appeared normal. These findings indicate that shrinkage of ocular dominance columns does not occur in humans with amblyopia caused by accommodative esotropia. The ocular dominance columns are probably no longer susceptible to shrinkage at the age when most children with this condition begin to develop amblyopia.

The effect of experimental strabismus on the development of vernier acuity and grating acuity was studied in Macaca nemestrina monkeys. Six monkeys were studied longitudinally beginning near 10 days after birth. Four of the six monkeys developed amblyopia. As is true for human strabismic amblyopes, the deficit in vernier acuity was larger than the deficit in grating acuity in the amblyopic monkeys. The developmental data reveal that this differential disruption of vernier acuity can be understood as a result of a slowed developmental process associated with amblyopia.

Amblyopia is usually considered to be a deficit in spatial vision. But there is evidence that amblyopes may also suffer specific deficits in motion sensitivity as opposed to losses that can be explained by the known deficits in spatial vision. We measured sensitivity to visual motion in random dot displays for strabismic and anisometropic amblyopic monkeys. We used a wide range of spatial and temporal offsets and compared the performance of the fellow and amblyopic eye for each monkey. The amblyopes were severely impaired at detecting motion at fine spatial and long temporal offsets, corresponding to fine spatial scale and slow speeds. This impairment was also evident for the untreated fellow eyes of strabismic but not anisometropic amblyopes. Motion sensitivity functions for amblyopic eyes were shifted toward large spatial scales for amblyopic compared to fellow eyes, to a degree that was correlated with the shift in scale of the spatial contrast sensitivity function. Amblyopic losses in motion sensitivity, however, were not correlated with losses in spatial contrast sensitivity. This, combined with the specific impairment for detecting long temporal offsets, reveals a deficit in spatiotemporal integration in amblyopia which cannot be explained by the lower spatial resolution of amblyopic vision.

When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.

Amblyopia is characterized by losses in a variety of aspects of spatial vision, such as acuity and contrast sensitivity. Our goal was to learn whether those basic spatial deficits lead to impaired global perceptual processing in strabismic and anisometropic amblyopia. This question is unresolved by the current human psychophysical literature. We studied contour integration and contrast sensitivity in amblyopic monkeys. We found deficient contour integration in anisometropic as well as strabismic amblyopic monkeys. Some animals showed poor contour integration in the fellow eye as well as in the amblyopic eye. Orientation jitter of the elements in the contour systematically decreased contour-detection ability for control and fellow eyes, but had less effect on amblyopic eyes. The deficits were not clearly related to basic losses in contrast sensitivity and acuity for either type of amblyopia. We conclude that abnormal contour integration in amblyopes reflects disruption of mechanisms that are different from those that determine acuity and contrast sensitivity, and are likely to be central to V1.

We examined cytochrome oxidase (CO) activity in striate cortex of four macaque monkeys after monocular enucleation at ages 1, 1, 5, and 12 weeks. These animal experiments were performed to guide our interpretation of CO patterns in occipital lobe specimens obtained from two children who died several years after monocular enucleation during infancy for tumor. In the macaques, the ocular dominance columns were labelled by injecting [3H]proline into the remaining eye. After enucleation at age 1 week, ocular dominance columns were eliminated in layer IVcβ, resulting in a uniform pattern of autoradiographic label and CO staining. However, columns could still be seen in wet, unstained sections and with the Liesegang silver stain. Autoradiographs through layers IVcα and IVa showed residual, shrunken columns belonging to the missing eye, indicating that enucleation has less drastic effects in these layers. In the two human cases, enucleation at age 1 week also resulted in uniform CO staining in layer IVc. In the macaque after enucleation at age 5 weeks, ocular dominance columns belonging to the missing eye were severely narrowed, but still occupied 20% of layer IVcβ. CO revealed wide, dark columns alternating with thin, pale columns in layer IVcβ. The CO pattern and the columns labelled by autoradiography matched perfectly. After enucleation at age 12 weeks, only mild shrinkage of ocular dominance columns occurred. Enucleation at ages 1, 5, and 12 weeks did not alter the pattern of thin-pale–thick-pale stripes in V2. The main findings from this study were that (1) CO histochemistry accurately labels the boundaries of columns in layer IVcβ of macaque striate cortex after early monocular enucleation, making it a suitable technique for defining the critical period for plasticity of ocular dominance columns in human striate cortex; (2) enucleation causes more severe shrinkage of ocular dominance columns than eyelid suture; (3) early monocular enucleation obliterates ocular dominance columns in layer IVcβ, but their pattern remains visible in wet sections and with the Liesegang stain; and (4) enucleation does not affect CO staining in V2.