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Query: UMLS:C0038379 (strabismus)
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Amblyopia can be induced by opacity of the ocular media (e.g., cataract), misalignment of the ocular axes (strabismus), or unequal refractive error in the eyes (anisometropia). Experiments in monkeys have shown that early monocular eyelid suture, a model of amblyopia caused by cataract, results in shrinkage of the eye's ocular dominance columns in striate cortex. This reduction of the geniculocortical projection from the deprived eye has been thought to explain in part the mechanism of amblyopia. We labeled the ocular dominance columns in monkeys with amblyopia by using cytochrome oxidase histochemistry. In animals rendered amblyopic by early unilateral eyelid suture, no pattern of cytochrome oxidase activity appeared in layer IVc. Outside layer IVc, alternating rows of light and dark patches were present; the pale patches fit in register with the shrunken ocular dominance columns of the deprived eye, which were labeled by autoradiography. Subsequent removal of one eye caused a striking cytochrome oxidase pattern to emerge in layer IVc that correlated precisely with the shrunken (deprived eye) and expanded (normal eye) ocular dominance columns. This correlation was shown by injecting one eye with [3H]proline. It has remained unsettled whether other forms of amblyopia are accompanied by shrinkage of ocular dominance columns. To address this issue, in an analogous clinical case, we examined the pattern of cytochrome oxidase activity in a human subject with a history of anisometropic amblyopia who suffered a lesion of one optic nerve shortly before death. The ocular dominance columns were normal in width, indicating that some forms of amblyopia occur without shrinkage of ocular dominance columns.
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PMID:Amblyopia induced by anisometropia without shrinkage of ocular dominance columns in human striate cortex. 839 Jun 68

The squirrel monkey is the only primate reported to lack ocular dominance columns. Nothing anomalous about the visual capacity of squirrel monkeys has been found to explain their missing columns, leading to the suggestion that ocular dominance columns might be "an epiphenomenon, not serving any purpose" (Livingstone et al., 1995). Puzzled by the apparent lack of ocular dominance columns in squirrel monkeys, we made eye injections with transneuronal tracers in four normal squirrel monkeys. An irregular mosaic of columns, averaging 225 microns in width, was found throughout striate cortex. They were double-labeled by placing wheat germ agglutinin-horseradish peroxidase into the left eye and [3H]proline into the right eye. The tracers labeled opposite sets of interdigitating columns, proving they represent ocular dominance columns. The columns were much clearer in layer IVc alpha (magno-receiving) than IVc beta (parvo-receiving). In the lateral geniculate body, the parvo laminae showed extensive mixing of ocular inputs, suggesting that increased label spillover contributes to the blurred columns in layer IVc beta. The cytochrome oxidase (CO) patches were organized into distinct rows, but they bore no consistent relationship to the ocular dominance columns. These experiments indicate that ocular dominance columns are less well segregated in squirrel monkeys than macaques, but they are present. This fact is pertinent to a recent study reporting that ocular dominance columns are absent in normal squirrel monkeys, but induced to form by strabismus (Livingstone, 1996).
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PMID:Anatomical demonstration of ocular dominance columns in striate cortex of the squirrel monkey. 875 63

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.
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PMID:Pattern of ocular dominance columns in human striate cortex in strabismic amblyopia. 887 Feb 33

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye's columns occupied more territory than the ipsilateral eye's columns, even in the central visual field representation (0 degree to 8 degrees), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 microns, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of six M. fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.
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PMID:Intrinsic variability of ocular dominance column periodicity in normal macaque monkeys. 892 31

Some models of visual cortical development are based on the assumption that the tangential organization of V1 is not determined prior to visual experience. In these models, correlated binocular activity is a key element in the formation of visual cortical columns, and when the degree of interocular correlation is reduced the models predict an increase in column spacing. To examine this prediction we measured the spacing of columns, as defined by cytochrome oxidase (CO) blobs, in the visual cortex of monkeys whose binocular vision was either normal or disrupted by a strabismus. The spatial distribution of blobs was examined in seven normal and five strabismic macaques. Tangential sections through the upper layers of the visual cortex were stained to reveal the two-dimensional (2D) pattern of CO blobs. Each blob was localized and their center-to-center spacing, packing arrangement and density were calculated using 2D nearest-neighbor spatial analyses. The mean center-to-center spacing of blobs (590 microm for normally reared and 598 microm for strabismic macaques) and the mean density of blobs (3.67 blobs/mm2 for normally reared and 3.45 blobs/mm2 for strabismic macaques) were not significantly different. In addition, the 2D packing arrangement of the blobs was not affected by strabismus. While it is clear that neural activity plays a key role in the elaboration and refinement of ocular dominance cortical modules, we conclude that it does not determine the spatial period of the pattern of CO blobs. This suggests that aspects of the neural circuitry underlying the columnar architecture of the visual cortex are established prenatally and its fundamental periodicity is not modifiable by experience.
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PMID:Spacing of cytochrome oxidase blobs in visual cortex of normal and strabismic monkeys. 961 18

Misalignment of the ocular axes induces double vision and rivalry. To prevent these unpleasant sensations, most subjects fixate preferentially with one eye and suppress entirely the deviating eye or else suppress portions of the visual field of either eye. To explore the mechanism of visual suppression, a divergent strabismus (exotropia) was induced in six normal, adult Macaca fascicularis by disinserting the medial rectus muscles. After 4-8 weeks, each animal was chaired to measure its exotropia and to determine its ocular fixation preference. Five of the monkeys developed a clearly dominant eye. It was injected with [(3)H]proline. Alternate sections from flat-mounts of striate cortex were then processed either for autoradiography to label the ocular dominance columns or for cytochrome oxidase (CO) to assess local metabolic activity. Two CO patterns were seen, often in the same cortex. The first consisted of thin dark columns alternating with wide pale columns. This pattern arose from reduced CO activity in the suppressed eye's monocular core zones and both eyes' binocular border strips. The second pattern consisted of thin pale bands from reduced metabolic activity in both eyes' border strips. The thin dark-wide pale CO pattern was more widespread in the three animals with a strong fixation preference. The dark CO columns usually fit in register with the ocular dominance columns of the fixating eye, suggesting that perception was suppressed in the deviating eye. In most animals, however, the correlation switched in peripheral cortex contralateral to the deviating eye, implying local suppression of the fixating eye's temporal retina (beyond 10 degrees), as reported in humans with divergent strabismus. In the two animals with a weak fixation preference, pale border strips were found within the central visual field representation in both hemispheres. This CO pattern was consistent with alternating visual suppression. These experiments provide the first anatomical evidence for changes in cortical metabolism that can be correlated with suppression scotomas in subjects with strabismus.
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PMID:Metabolic mapping of suppression scotomas in striate cortex of macaques with experimental strabismus. 1043 65

Strabismus induces an abnormal pattern of alternating light and dark columns of cytochrome oxidase (CO) activity in macaque striate cortex. This pattern may arise because visual perception is suppressed in one eye to avoid diplopia. To test whether CO activity is reduced in the ocular dominance columns of the suppressed eye, we performed monocular enucleation to co-label the ocular dominance columns with Zif268 immunohistochemistry in seven exotropic adult Macaca fascicularis. This approach was unsuccessful, for two reasons. First, Zif268 yielded inconsistent labelling, that was usually greater in the enucleated eye's ocular dominance columns, but was sometimes greater in the intact eye's columns. Therefore, Zif268 was not a reliable method for identifying the ocular dominance columns serving each eye. Second, in three control animals we found that a brief survival period following monocular enucleation (needed for Zif268 levels to change) was long enough to alter CO staining. For example, a survival time of only 3 h was sufficient to induce CO columns, indicating that the activity of this enzyme fluctuates more rapidly than realized previously. Independent of these findings, we have also discovered that acute monocular enucleation produces a vivid pattern of ocular dominance columns visible in unstained or CO-stained sections under dark-field illumination. The ocular dominance columns of the acutely enucleated eye appear dark. This was verified by labelling the ocular dominance columns with [3H]proline. Dark-field illumination of the cortex after acute monocular enucleation offers a new, easy method for identifying the ocular dominance columns in macaques.
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PMID:Rapid identification of ocular dominance columns in macaques using cytochrome oxidase, Zif268, and dark-field microscopy. 1101 71

Strabismus, a misalignment of the eyes, results in a loss of binocular visual function in humans. The effects are similar in monkeys, where a loss of binocular convergence onto single cortical neurons is always found. Changes in the anatomical organization of primary visual cortex (V1) may be associated with these physiological deficits, yet few have been reported. We examined the distributions of several anatomical markers in V1 of two experimentally strabismic Macaca nemestrina monkeys. Staining patterns in tangential sections were related to the ocular dominance (OD) column structure as deduced from cytochrome oxidase (CO) staining. CO staining appears roughly normal in the superficial layers, but in layer 4C, one eye's columns were pale. Thin, dark stripes falling near OD column borders are evident in Nissl-stained sections in all layers and in immunoreactivity for calbindin, especially in layers 3 and 4B. The monoclonal antibody SMI32, which labels a neurofilament protein found in pyramidal cells, is reduced in one eye's columns and absent at OD column borders. The pale SMI32 columns are those that are dark with CO in layer 4. Gallyas staining for myelin reveals thin stripes through layers 2-5; the dark stripes fall at OD column centers. All these changes appear to be related to the loss of binocularity in cortical neurons, which has its most profound effects near OD column borders.
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PMID:Effects of experimental strabismus on the architecture of macaque monkey striate cortex. 1155 Jan 74

To describe the structural basis for lack of binocular fusion in strabismic primates, we investigated intrinsic horizontal connections within striate cortex (area V1) of normal and strabismic, adult macaque monkeys. The strabismic animals had early-onset natural esotropia (the visual axes deviated nasally), normal visual acuity in each eye, and the constellation of ocular motor deficits that typify human infantile strabismus. Horizontal patchy connections and synaptic boutons were labeled by injections of the neuronal tracer biotinylated dextran amine. Ocular dominance columns (ODCs), and blob vs. interblob compartments, were revealed by using cytochrome oxidase (CO). In layers 2/3 and 4B of the strabismic monkeys, patchy projections and boutons terminated much more frequently in same-eye (73%) as opposed to opposite-eye (27%) ODCs (normal monkeys 58% and 42%, respectively). The deficiency of binocular connections in the strabismic cortex was evident qualitatively as a "skip" pattern, in which every other row of ODCs had labeled patches. Analysis of V1 in normal monkeys revealed that the deficits in strabismic V1 were due mainly to a loss of binocular connections between neurons in CO-interblob compartments. In both normal and strabismic monkeys: (1) CO-blob compartment neurons showed a more pronounced bias for monocular connectivity, and (2) commitment of connections to the same CO-compartment as the injection site (blob-to-blob, or interblob-to-interblob) was moderately strong (64%) but far from absolute. These findings help elucidate the relative roles of visual experience vs. innate mechanisms in the development of axonal connections between ocular dominance domains and compartments within macaque V1. They also provide the first detailed description of the V1 maldevelopments associated with unrepaired natural, infantile-onset strabismus in primates.
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PMID:Paucity of horizontal connections for binocular vision in V1 of naturally strabismic macaques: Cytochrome oxidase compartment specificity. 1516 26

Human striate cortex contains an orderly map of the contralateral visual field, which is distorted to make a disproportionate amount of tissue available for the representation of the macula. Engrafted on the retinotopic map is a system of alternating inputs known as ocular dominance columns. These columns consist of interleaved bands of geniculocortical afferents in layer 4C serving either the right eye or the left eye. They can be revealed in humans with a history of prior visual loss in one eye by processing striate cortex for cytochrome oxidase at autopsy. Because their geniculate input is segregated, cells within ocular dominance columns in layer 4C respond to stimulation of one eye only. These monocular cells converge onto binocular cells in other layers, integrating signals from the two eyes. The columns in humans appear similar to those found in many primate species, including the macaque. In the squirrel monkey, however, the occurrence of ocular dominance columns is highly variable. Some squirrel monkeys lack columns, yet they seem to have no impairment of visual function. In animals with weakly expressed columns, one can detect a cortical pattern of metabolic activity corresponding to retinal blood vessels. It appears because visual deprivation from shadows cast by blood vessels induces remodeling of geniculocortical afferents, in a manner akin to the shrinkage of ocular dominance columns from congenital cataract. Although the function of ocular dominance columns is unknown, their metabolism is altered in strabismus, suggesting a role in visual suppression.
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PMID:Ocular integration in the human visual cortex. 1750 56


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