September 2004
Volume 45, Issue 9
Free
Eye Movements, Strabismus, Amblyopia and Neuro-ophthalmology  |   September 2004
Ocular Dominance Column Width and Contrast Sensitivity in Monkeys Reared with Strabismus or Anisometropia
Author Affiliations
  • Morris L. J. Crawford
    From the Department of Ophthalmology and Visual Science, University of Texas Health Science Center at Houston, Houston, Texas; and the
  • Ronald S. Harwerth
    College of Optometry, University of Houston, Houston, Texas.
Investigative Ophthalmology & Visual Science September 2004, Vol.45, 3036-3042. doi:https://doi.org/10.1167/iovs.04-0029
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Morris L. J. Crawford, Ronald S. Harwerth; Ocular Dominance Column Width and Contrast Sensitivity in Monkeys Reared with Strabismus or Anisometropia. Invest. Ophthalmol. Vis. Sci. 2004;45(9):3036-3042. https://doi.org/10.1167/iovs.04-0029.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

purpose. To study the relationship between the width of ocular dominance columns in primary visual cortex and spatial contrast sensitivity functions in monkeys with strabismus or anisometropia during infancy.

methods. Adult monkeys having had monocular visual abnormalities induced in infancy were tested behaviorally for spatial contrast sensitivity and then subjected to functional enucleation of one eye to reveal the ocular dominance columns (ODCs) of the primary visual cortex by cytochrome oxidase (CO) staining. The relative widths of the left and right eyes’ ODCs were measured and related to the contrast sensitivity functions.

results. The relative widths of the ODCs having input from eyes with strabismic or anisometropic amblyopia were reduced in proportion to the age of onset and the duration of the early visual abnormality. The relative losses in contrast sensitivity were in ordinal agreement with the losses in relative width of the ODCs.

conclusions. Amblyopia induced by the early monocular abnormalities of strabismus or anisometropia is proportional to the loss in cortical afference as reflected in the reduction in width of the respective ODCs in the primary visual cortex.

Over the past 50 years, visual neuroscience has provided a neural basis for the clinical consequences of visual defects that occur during infancy, a phenomenon well known to the ophthalmic clinician throughout medical history. 1 The site of the initial neural defect of amblyopia has been shown to be in the primary visual cortex 2 3 4 with functional aspects of visual processing being relatively normal in more peripheral sites. 5 The nature of the neural defect is in the failure of the afflicted eye to maintain and strengthen synaptic control over cortical neurons. The afferent ocular pathway connections to the input layer 4C of visual cortex, present at birth, 6 7 are normally balanced to divide the dominant control over primary recipient cortical neurons (and higher order neurons) rather equally between the two eyes, with the majority of cortical neurons being binocular by having synaptic afferent connections from both eyes. An infant eye that is disadvantaged by having a poor quality of retinal image (e.g., cataract, strabismus, or anisometropia) cannot sustain these synaptic connections and loses command over a critical share of cortical neurons, a condition sufficient to explain the associated amblyopia. A metabolic and anatomic correlate of this synaptic failure is the relative shrinkage of the ocular dominance domain, or column (ODC), associated with the defective eye. 7 The current report describes a study to determine whether changes in ODC width are related to the psychophysical loss of contrast sensitivity (CS) in adult monkeys that had been subjected to early abnormal binocular vision from experimental strabismus or anisometropia during infancy. 
Methods
Six infant macaque monkeys (Macaca mulatta) were used, according to the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (revised, 1986) and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The research protocols were reviewed and approved by the University of Houston and The University of Texas—Houston, Institutional Animal Care and Use Committees. Monocular anisometropia was induced by having the monkeys wear contact lenses of different power in one eye, thereby inducing a monocular image blur. 8 Monkey HIG wore a −3-D lens continuously on the right eye beginning at 14 days of age and lasting for 60 days. Monkey HT1 wore the same power (−3-D) lens from 21 to 133 days of age. Monkey ELL wore a −10-D lens from 14 to 134 days of age. Monkey MIK wore a −10-D lens from 28 to 88 days of age. 
Surgical esotropia was initiated in the remaining two monkeys. Under ketamine HCl anesthesia, the lateral rectus muscle of the right eye was extirpated, and a tuck in the medial rectus shortened the muscle by ∼1 mm, inducing esotropia. 9 Monkey DAR underwent surgery at 1 month of age, whereas monkey TRX was operated on at a later age (6 months). A caveat regarding this methodology is that it is not known what duration, and to what degree, the esotropia was sustained over the next 2 years, as the infants remained with their mothers in an outdoor colony. However, on delivery to the laboratory at 24 months of age, the degree of residual esotropia was undetectable. Monkey PT served as a normally reared control (Table 1)
After the experimental treatment during infancy, several of the monkeys were trained and tested to measure their spatial CS functions between 2 and 4 years of age, according to our previously described methods. 10 11 12 13 At approximately 5 years of age, the monkeys were assigned to an experimental glaucoma project where intraocular pressure was raised in one eye, leading (over a period of 6–25 months) to the death of ganglion cells. This functional enucleation permitted subsequent marking of the ODCs in the primary visual cortex, using the histochemical staining technique for cytochrome oxidase (CO) described by Wong-Riley. 14  
In preparation for the histochemistry, the brains were flushed with saline and fixed in a 4% paraformaldehyde solution, in situ, then removed and cryoprotected through a sucrose series (10%, 20%, and 30%), frozen, and 30-μm-thick tangential sections of the brain’s visual cortices were stained for CO, mounted on gelatinized slides, dehydrated, and coverslipped. The images of the brain tissue were captured through a microscope (Stemi SV11; Carl Zeiss Meditec, Dublin, CA) microscope with a digital camera (DMC-1; Polaroid, Cambridge, MA) digital camera with image-analysis software (PhotoShop; Adobe, Mountain View, CA). From these images, the ODCs of the V1 layer 4C were easily identified by the CO-dark stripes representing input from neurons of the normal eye, whereas the interdigitated CO-pale stripes represented input from the experimental eye. 
Results
Figure 1A shows the ODCs from layer 4C of the normal monkey (PT) to be of approximately the same average width, as has been reported before for six normal adult cynomolgus monkeys. 7 The inset indicates the approximate area from which the sample was taken. The white rectangles illustrate a typical scan path for quantifying the cytochrome oxidase reactivity (COR) in the ODCs of all monkeys. Multiple optical density scans were made of 10 pairs of ODCs in layer 4C of the V1 cortex, representing central and paracentral visual space. 15 16 17 Scans (10 pixels in width) were made orthogonal to the long axis of the ODC. The scans began in the center of one ODC, traversed the adjacent ODC to end in the center of the next ODC. The comparison scans were taken at the same location but shifted to start in the adjacent column. Each scan profile was subjected to a 3-point rolling averaging procedure to reduce pixel-to-pixel variation (the bright holes in the image are empty blood vessels and represent a source of noise). The 10 scans were normalized to the center of the column, and the average ODC density profile (±1 SD) was then computed. The bottom of Figure 1 is a graph of the average COR for the left and right (functional enucleate) eyes of the control monkey. The half-amplitude of the slope of the mean density change between the CO-dark and the CO-pale ODC (as judged by eye) was used to define the ODC border and subsequently to determine the relative ODC widths. Note that the ratio of the averaged right-eye ODC width to the averaged left-eye ODC width for the normal monkey PT is approximately 1.0. Normally, the area and relative widths of macaque ODCs in layer 4C representing central and paracentral vision are approximately the same in each eye. For example, Horton and Hocking 7 found an average difference between ODCs of 8% ± 4%. In our example, the measured average difference in width was less than 2%. 
Figure 2 presents sample ODC patterns for the six experimental monkeys. The CO-dark ODC represents input from the normal eye, whereas the CO-pale ODC represents the input from the experimental eye. The inset indicates the approximate cortical area where the samples were taken. In each of the illustrations, the ODC innervated by the defocused or deviated experimental eye (pale ODC) was significantly narrower than the companion ODC with connections with the normal eye, suggesting a significant shift in the cortical neuronal control exercised by the two eyes. Because normal ODCs in macaques are generally of average equal width, the effect of the experimental manipulation can be quantified by the degree of change in the relative ODC widths. The normalized average COR density profiles from which the average width of the ODC was estimated are shown in Figure 3
Experimental Anisometropia
The lens-reared monkeys were treated for different periods starting at different ages, and all the treatments reduced the width of the ODC that had input from the lens-treated eye. Experimental anisometropia induced with a −3-D lens in monkeys HIG and HT1 (Figs. 2A 2B) was started at 2 and 3 weeks of age, respectively. Figure 3A shows that a shorter 60-day period of relatively mild −3-D monocular blur resulted in an average reduction of 27% of the ODC width for input from the lens-treated eye. In comparison, Figure 3B shows that the same magnitude of defocus started 1 week later, but lasted for a longer duration (112 days), resulting in a slightly larger difference (32%) in the average ODC width with input from the treated eye. 
A more severe monocular defocus, induced by a −10-D lens in monkeys MIK and ELL (Figs. 3C 3D) , resulted in a significantly larger reduction in width of the ODCs associated with the treated eye. Monkey MIK wore the contact lens from 30 to 88 days of age, producing a 53% reduction in ODC width (shown in Fig. 3C ). Monkey ELL (Fig. 3D) who wore the −10-D lens from 14 to 134 days of age had a larger average shrinkage of 62% in the associated ODCs. Therefore, defocusing the visual input to one eye during the first month of life resulted in a permanent large shift in the relative widths of the ODCs in favor of the normal eye, with the greater shift in relative width associated with a greater degree of blur. The results of these four experimental anisometropia experiments suggest that the greater the optical blur and the longer the duration of the blur, the greater the shift in the relative widths of ODCs to the detriment of the treated eye—results that are consistent with our previous behavioral findings. 18  
Experimental Surgical Esotropia
Similar effects were found for two infant monkeys that were subjected to surgical esotropia at different ages. DAR (Figs 2E 3E) , made esotropic at 30 days of age, showed a substantial reduction of the ODC width, with a 0.42 ratio for the deviated to fixating eyes, or a 58% loss in relative width (Fig. 3E) . The second monkey, TRX, in which surgical esotropia was started at a later age (6 months), showed somewhat less effect on the ODC widths, with a 40% reduction from normal (Fig. 3F) . Assuming that ODCs were of the same average width at the beginning (as shown in Fig. 1 ) monocular esotropia initiated during the first 6 months of life produced a dramatic, permanent shift in the relative eye dominance over neurons in primary visual cortex. 
Contrast Sensitivity
Some of the monkeys had been tested for spatial CS of the two eyes at approximately 2 years of age (see Refs. 10 11 12 13 , 18 for methodology). Figure 4 illustrates the CS functions from the normal monkey (PT; Fig. 4A ), in which the peak sensitivity is approximately 2 cyc/deg and with a high spatial frequency limit of approximately 35 cyc/deg. In addition, the monocular functions (open circles and squares) are virtually identical, while the binocular function (diamonds) shows a higher overall sensitivity that is typical of normal binocular summation. 11 Therefore, in the normal monkey, equality in ODC width is associated with equality in monocular CS and an enhanced sensitivity with binocular, compared with monocular, viewing. Figures 4B 4C 4D 4E present CS measurements from three of the anisometropic monkeys and one of the strabismic monkeys, TRX, for comparison with the sensitivity of the normal monkey data in Figure 4A . For HT-1, the monkey subjected to mild −3-D monocular blur during infancy (Fig. 4B) , the monocular CS of the treated eye (circles) is only slightly, and insignificantly, less than the untreated eye (squares)—that is, the sensitivities of the two eyes are nearly the same, even though the V1 ODC widths were reduced by 32% of normal (see Fig. 3B ). In contrast, both animals reared with −10-D of defocus demonstrated highly compromised spatial contrast sensitivities over the middle and high spatial frequencies. Figures 4C and 4D shows the impact of the greater blur by a −10-D lens for MIK and ELL, respectively, in which the large loss in sensitivity, especially for the higher spatial frequencies, reduced the high spatial resolution limit from approximately 32 cyc/deg to approximately 8 cyc/deg. This change in sensitivity was associated with a 53% loss in V1 ODC width (Fig. 3C) . The results for ELL (Fig. 3D) were similar, for both spatial vision (a relative sensitivity loss from 32–9 cyc/deg.) and in ODC width (a 62% loss in ODC width). 
Figure 3E shows the monocular CS functions from TRX to be virtually identical, despite the demonstrated 40% reduction of the width of the ODC associated with the surgically deviated esotropic eye (see the Discussion section). 
In summary, these psychophysical results demonstrate that monocular blur during infancy produces a loss in CS associated with an ordinal reduction in ODC width, although the relationship between sensitivity loss and neuronal control appears to be nonlinear. 
Discussion
There are few data in the literature relating the behavioral sensitivity of a mammalian sensory system to the number of cortical neurons supporting that sensitivity. The present experiments show that it is feasible, although additional experiments will be necessary to define the functional relationships fully. For example, the change in the relative widths of the ODCs can be related to the numbers of V1 neurons that serve the two eyes. Hendry et al. 19 calculated the average numbers of neurons beneath a 1-mm2 patch of V1 cortex in five normal adult cynomolgus monkeys to be 126,120 ± 5.3/mm2, twice the neuronal density of tissue in other cortical areas. Assuming that Macaca fascicularis and M. mulatta have the comparable neuronal densities, in their normal hypercolumns (a left and right ODC pair) of approximately 1 mm in width, 3 each eye within a hypercolumn would have synaptic dominance over slightly more than 60,000 neurons/mm2 (mostly monocular neurons in layer 4C). Therefore, a 32% reduction in the width of an ODC would translate into a functional loss of some ∼19,000/mm2 neurons throughout the full cortical thickness. It is interesting that whereas monkey HT-1 showed a 32% reduction in cortical ODC width (and a presumed loss of control over as many as 19,000 neurons), there was only a minor change in CS. In comparison, the more severe blur experienced by monkeys MIK and ELL induced nearly twice the reduction in ODC space (53% and 62%, and correspondingly, an estimated loss of ∼32,000 and ∼37,000 neurons/mm2 throughout the translaminar column) with that loss associated with a significantly greater impact on the balance in CS between the two eyes. One might expect there to be a threshold effect (i.e., that some critical number of neurons would be lost before a psychophysical change in CS could be detected using our threshold methodology). Moreover, the numbers of neurons lost before a behavioral defect could be exposed may be quite large. For example, we 20 and others, 21 have described such a phenomenon for the relationship between the loss of retinal ganglion cells and the appearance of a visual field defect in glaucoma, where as many as half the ganglion cells have become dysfunctional and died before a defect appears in the clinical visual field measurement. If a similar rationale is applied to these experiments on anisometropia, the threshold for a detectable loss in CS must be a functional loss in excess of ∼20,000 V1 neurons. With a neuronal loss greater than ∼30,000 such neurons, there is a dramatic loss in CS. Obviously, additional experiments are required to determine the full functional relationship between the numbers of V1 neurons required for a criterion level of CS. However, these few data point to the clear possibility of the quantification of the functional relationship between visual sensitivity and the number of cortical neurons. 
The CS results from the esotropic monkey TRX may at first glance appear to be incompatible with the change in ODC width (i.e., a large 40% loss in ODC width but no significant change in CS), whereas larger losses of 53% and 62% by monocular image blur showed a decided loss in CS. Therefore, one might argue that the threshold for altering CS requires a neuronal loss of between 40% and 53% of V1 neurons. However, as previously reported, 22 TRX (SM184) had severe defects in functions associated with binocular visual neurons. In that earlier paper, TRX was shown to have significant impairment of binocular sensitivity, whereas eye alignment, motor fusion, and oculomotor responses were within the range of normal monkeys. These results suggest that (1) the most important loss in neuronal control occurred in the “border strips” of the ODC containing the binocular neurons and (2) that monocular CS functions are largely dependent on functions of neurons in the central monocular “core zone” of the ODC-neuronal losses sufficient to reduce stereoscopic, but not CS functions (see Horton and Hocking 23 for a description of these two components of the ODC). 
Kiorpes et al. 24 have compared single-unit recording from V1 cortex with CS functions in strabismic and anisometropic amblyopic monkeys. Their results were consistent with the results reported herein. The severity of the amblyopia, as indicated from the CS functions, was related to the degree of shift in cortical eye dominance (i.e., loss of control over cortical neuronal space). 
On the other hand, Fenstemaker et al. 25 failed to find a significant shift in the relative ODC widths in two esotropic Macaca nemestrina, although they did report changes reflecting a lack of normal binocular activation at the boundaries between ODCs. However, they stated that both animals alternated in fixation and showed no evidence of amblyopia—factors mitigating a shift in relative ODC widths. 
The results of the present study show that ODC widths in V1 undergo functional shifts, with the normal ODC retaining control over cortical neuronal space, as there is a complementary decrease in neuronal space influenced by the impaired eye. The degree of ODC shift is related not only to the sort of visual abnormality, but also to the manner in which the animal responds to the abnormality. For example, the pattern of fixation is thought to determine the degree to which this shift in cortical eye dominance is affected. Adopting a constant unilateral fixation pattern (common in the case of unilateral esotropia), the deviating, nonfixating eye most frequently develops amblyopia. In contrast, monkeys or humans with exotropia and divergent visual axes often adopt an alternating fixation pattern, thereby stimulating and keeping intact the monocular neural connections within the cortex. 1 26 27 28 In the current experiment using surgical esotropia, the former condition is speculated to have occurred—that is, the monkey (DAR) adopted a unilateral fixation pattern, inducing a functional binocular neuronal disconnect of the esotropic eye from the brain, with a concomitant shift in the control of cortical space (the ODC) in favor of the normal eye. 23 However, the CSF was virtually identical in the two eyes of monkey TRX, consistent with a pattern of alternating fixation sufficient to reduce binocular functions, but not sufficient to reduce the function of the ODC monocular neuronal core. This interpretation emphasizes the spatial specialization of the ODC, where the central monocular core supports monocular CS functions and retains functional integrity in the face of a substantial (>40%) reduction in cortical space, whereas, the binocular zones of the ODC support stereoscopic functions and are readily degraded with the loss of cortical space. 
The foregoing analysis describes the relative spatial shift in eye dominance over neurons of the primary visual cortex and relates that shift to the psychophysical sensitivity. This spatial shift is manifest in the relative area of cortex (and consequently, the numbers of cortical neurons) devoted to each of the two eyes and does not obligate a change in the spatial frequency of the pattern itself. However, in the literature there is a continuing and frequent confusion of the shift in relative ODC width with a change in ODC spacing. A host of studies have sought some change in the ODC basic spatial frequency after abnormal ocular conditions during infancy. Some have reported an increase in the inter-ODC spacing, 29 30 whereas others have failed to find any such change. 31 32 It is important to re-emphasize that (as originally described, empirically and theoretically, in several studies 2 3 4 33 [Jones DG, et al. IOVS 1996;37:ARVO Abstract 1964] from microelectrode recordings) it is the relative numeric control over cortical visual neurons indicated by the relative cortical area (and ODC width) that is altered by abnormal early visual experience, and it occurs without an obligate change in ODC spacing. Although differences in ODC spatial frequency occur within the cortices of individual animals, 3 34 between animals, 3 and between mammalian species, 35 these variations in ODC spacing have yet to be incorporated within any theoretical functional framework of visual information processing. 
 
Table 1.
 
Summary of the Individual Animal Treatments
Table 1.
 
Summary of the Individual Animal Treatments
Monkey Treatment Beginning Age of Treatment (d) Ending Age of Treatment (d)
DAR Surgical esotropia 30
TRX Surgical esotropia 182
ELL −10-D lens 14 134
MIK −10-D lens 28 88
HT1 −3-D lens 21 133
HIG −3-D lens 14 74
PT Normal control
Figure 1.
 
An illustration of the method of scanning the optical density of the COR over the width of the ODC. Top: the scan path (rectangles) was 10 pixels wide and orthogonal to the long axis of the columns and selected to minimize inclusion of the many blood vessels. Bottom: the average profile of 10 scans each over the CO-dark and CO-pale ODC of the normal monkey cortex (PT) aligned for comparison of the relative widths. Note that the columns are of the same average width estimated by the perpendicular line drawn from the half-amplitude density transition from the dark to the pale columns.
Figure 1.
 
An illustration of the method of scanning the optical density of the COR over the width of the ODC. Top: the scan path (rectangles) was 10 pixels wide and orthogonal to the long axis of the columns and selected to minimize inclusion of the many blood vessels. Bottom: the average profile of 10 scans each over the CO-dark and CO-pale ODC of the normal monkey cortex (PT) aligned for comparison of the relative widths. Note that the columns are of the same average width estimated by the perpendicular line drawn from the half-amplitude density transition from the dark to the pale columns.
Figure 2.
 
Samples of layer 4C ODC patterns from the six experimental monkeys. Insets: the cortical location from which the ODC example was drawn, as well as where the scan profiles of Figure 3 were made. Example of ODCs for monkeys (A) HIG, (B) HT1, (C) MIK, (D) ELL, (E) DAR, and (F) TRX. The magnification of these images is unspecified and different between panels. The panel order in Figures 2 and 3 are the same.
Figure 2.
 
Samples of layer 4C ODC patterns from the six experimental monkeys. Insets: the cortical location from which the ODC example was drawn, as well as where the scan profiles of Figure 3 were made. Example of ODCs for monkeys (A) HIG, (B) HT1, (C) MIK, (D) ELL, (E) DAR, and (F) TRX. The magnification of these images is unspecified and different between panels. The panel order in Figures 2 and 3 are the same.
Figure 3.
 
Average COR profiles from which the relative ODC widths were estimated for the six experimental monkeys. Each graph shows the average density profile for 10 CO-dark (normal eye) and companion CO-pale (experimental eye) columns. The profiles have been normalized in the x-axis for the column centers, with no adjustment in the y-axis dimension. The ratio of widths, estimated from the half-amplitude transition between the CO-dark and CO-pale columns shows the ODC associated with the experimental eye to be narrower than that of the ODC for the normal companion eye. Monkeys (A) HIG, −3-D blur, 27% loss in relative ODC width; (B) HT1, −3-D blur, 32% loss in relative ODC width; (C) MIK, −10-D blur, 53% loss in relative ODC width; (D) ELL, −10-D blur, 62% reduction in relative ODC width; (E) DAR, surgical esotropia at 3 weeks, 58% reduction in relative ODC width; and (F) TRX, surgical esotropia at 6 months, 40% reduction in relative ODC width.
Figure 3.
 
Average COR profiles from which the relative ODC widths were estimated for the six experimental monkeys. Each graph shows the average density profile for 10 CO-dark (normal eye) and companion CO-pale (experimental eye) columns. The profiles have been normalized in the x-axis for the column centers, with no adjustment in the y-axis dimension. The ratio of widths, estimated from the half-amplitude transition between the CO-dark and CO-pale columns shows the ODC associated with the experimental eye to be narrower than that of the ODC for the normal companion eye. Monkeys (A) HIG, −3-D blur, 27% loss in relative ODC width; (B) HT1, −3-D blur, 32% loss in relative ODC width; (C) MIK, −10-D blur, 53% loss in relative ODC width; (D) ELL, −10-D blur, 62% reduction in relative ODC width; (E) DAR, surgical esotropia at 3 weeks, 58% reduction in relative ODC width; and (F) TRX, surgical esotropia at 6 months, 40% reduction in relative ODC width.
Figure 4.
 
CS functions (CSFs) for the normal monkey (PT; A) and for four of the experimental monkeys. (A) The monocular CSFs of the left and right eyes of the normal monkey are indicated by the square and circle data points, whereas the diamond data points (A) represent the binocular CSF, showing the superior sensitivity of binocular summation. (B) CSFs for monkey HT1, subjected to −3-D blur that induced only a modest reduction in peak sensitivity. (C) Monocular blur of −10 D in MIK induced a severe reduction in CSF at all spatial frequencies. (D) Monocular blur of −10 D in monkey ELL had the same effect as in (C). (E) CSFs are normal and virtually identical for the two eyes in strabismus monkey TRX.
Figure 4.
 
CS functions (CSFs) for the normal monkey (PT; A) and for four of the experimental monkeys. (A) The monocular CSFs of the left and right eyes of the normal monkey are indicated by the square and circle data points, whereas the diamond data points (A) represent the binocular CSF, showing the superior sensitivity of binocular summation. (B) CSFs for monkey HT1, subjected to −3-D blur that induced only a modest reduction in peak sensitivity. (C) Monocular blur of −10 D in MIK induced a severe reduction in CSF at all spatial frequencies. (D) Monocular blur of −10 D in monkey ELL had the same effect as in (C). (E) CSFs are normal and virtually identical for the two eyes in strabismus monkey TRX.
The authors thank Gunter K. von Noorden, MD, and Earl Smith, OD, PhD, for contributions in the treatment and testing of the animals. 
Von Noorden GK, Campos EC. Binocular Vision and Ocular Motility: Theory and Management of Strabismus. 2002; 6th ed. 512–513. Mosby St. Louis.
Wiesel TN, Hubel DH. Ordered arrangement of orientation columns in monkeys lacking visual experience. J Comp Neurol. 1974;158:307–318. [CrossRef] [PubMed]
Hubel DH, Wiesel TN, LeVay S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Lond B Biol Sci. 1977;278:377–409. [CrossRef] [PubMed]
LeVay S, Wiesel TN, Hubel DH. The development of ocular dominance columns in normal and visually deprived monkeys. J Comp Neurol. 1980;191:1–51. [CrossRef] [PubMed]
Blakemore C, Vital-Durand F. Effects of visual deprivation on the development of the monkey’s lateral geniculate nucleus. J Physiol. 1986;380:493–511. [CrossRef] [PubMed]
Rakic P. Prenatal development of the visual system in rhesus monkey. Philos Trans R Soc Lond [Biol]. 1977;278:245–260. [CrossRef]
Horton JC, Hocking DR. Intrinsic variability of ocular dominance column periodicity in normal macaque monkeys. J Neurosci. 1996;16:7228–7339. [PubMed]
Hung LF, Smith EL, III. Extended-wear, soft, contact lenses produce hyperopia in young monkeys. Optom Vis Sci. 1996;73:579–584. [CrossRef] [PubMed]
Von Noorden GK, Dowling JE. Experimental amblyopia in monkeys: II. Behavioral studies in strabismus amblyopia. Arch Ophthalmol. 1970;84:215–220. [CrossRef] [PubMed]
Harwerth RS, Crawford MLJ, Smith EL, III, Boltz RL. Behavioral studies of stimulus deprivation amblyopia in monkeys. Vision Res. 1981;21:779–789. [CrossRef] [PubMed]
Harwerth RS, Smith EL, III, Boltz RL, Crawford MLJ, Von Noorden GK. Behavioral studies of the effects of abnormal early visual experience in monkeys: spatial modulation sensitivity. Vision Res. 1983;23:1501–1510. [CrossRef] [PubMed]
Harwerth RS, Smith RL, III. The rhesus monkey as a model for normal vision of humans. Am J Optom Physiol Optics. 1985;62:633–641. [CrossRef]
Harwerth RS, Smith EL, III, Duncan GC, Crawford MLJ, Von Noorden GK. Multiple sensitive periods in the development of the primate visual system. Science. 1986;232:235–238. [CrossRef] [PubMed]
Wong-Riley M. Changes in the visual system of monocularly sutured or enucleated kittens demonstrable with cytochrome oxidase histochemistry. Brain Res. 1979;171:11–28. [CrossRef] [PubMed]
Daniel PM, Whitteridge D. The representation of the visual field on the cerebral cortex in monkeys. J Physiol Lond. 1961;159:203–221. [CrossRef] [PubMed]
Rolls ET, Cowey A. Topography of the retina and striate cortex and its relationship to visual acuity in the rhesus monkeys and squirrel monkeys. Exp Brain Res. 1970;10:298–310. [PubMed]
Tootell RHB, Switkes E, Silverman MS, Hamilton SLJ. Functional anatomy of macaque striate cortex. II. Retinotopic organization. J Neurosci. 1988;8:1531–1568. [PubMed]
Smith EL, III, Harwerth RS, Crawford MLJ. Spatial contrast sensitivity deficits in monkeys produced by optically induced anisometropia. Invest Ophthalmol. 1985;26:330–342.
Hendry SHC, Schwark HD, Jones EG, Yan J. Numbers and proportions of GABA-Immunoreactive neurons in different areas of monkey cerebral cortex. J Neurosci. 1987;7:1503–1519. [PubMed]
Harwerth RS, Carter-Dawson L, Shen F, Smith EL, III, Crawford MLJ. Ganglion cell losses underlying visual field defects from experimental glaucoma. Invest Ophthalmol Vis Sci. 1999;40:2242–2250. [PubMed]
Quigley HA, Dunkelberger GR, Green WR. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol. 1989;107:453–464. [CrossRef] [PubMed]
Harwerth RS, Smith EL, III, Crawford MLJ, von Noorden GK. Stereopsis and disparity vergence in monkeys with subnormal binocular vision. Vision Res. 1997;37:483–493. [CrossRef] [PubMed]
Horton JC, Hocking DR. Monocular core zones and binocular border strips in primate striate cortex revealed by the contrasting effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase activity. J Neurosci. 1998;18:5433–5455. [PubMed]
Kiorpes L, Kiper DC, O’Keefe LP, Cavanaugh JR, Movshon JA. Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia. J Neurosci. 1998;18:6411–6424. [PubMed]
Fenstemaker SB, Kiorpes L, Movshon JA. Effects of experimental strabismus on the architecture of macaque monkey striate cortex. J Comp Neurol. 2001;438:300–317. [CrossRef] [PubMed]
Sireteanu R. Binocular vision in strabismic humans with alternating fixation. Vision Res. 1982;22:889–896. [CrossRef] [PubMed]
Steinbach MJ. Alternating exotropia: temporal course of the switch in suppression. Invest Ophthalmol Vis Sci. 1981;20:129–133. [PubMed]
van Leeuwen AF, Collewijn H, de Faber JTHN, van der Steen J. Saccadic binocular coordination in alternating exotropia. Vision Res. 2001;41:3425–3435. [CrossRef] [PubMed]
Löwel S. Ocular dominance column development: strabismus changes the spacing of adjacent columns in cat visual cortex. J Neurosci. 1994;14:7451–7468. [PubMed]
Tieman SB, Tumosa N. Alternating monocular exposure increases spacing of ocularity domains in area 17 of cats. Vis Neurosci. 1997;14:929–938. [CrossRef] [PubMed]
Rathjen S, Schmidt KE, Löwel S. Two-dimensional analysis of the spacing of ocular dominance columns in normally raised and strabismic kittens. Exp Brain Res. 2002;145:158–165. [CrossRef] [PubMed]
Crawford MLJ. Column spacing in normal and visually deprived monkeys. Exp Brain Res. 1998;123:282–288. [CrossRef] [PubMed]
Hubel DH, Wiesel TN. Receptive fields of cells in striate cortex of very young, visually inexperienced kittens. J Neurophysiol. 1963;26:994–1002. [PubMed]
Kaschube M, Wolf F, Puhlmann , et al. The pattern of ocular dominance columns in cat primary visual cortex: intra- and interindividual variability of column spacing and its dependence on genetic background. Eur J Neurosci. 2003;18:3251–3266. [CrossRef] [PubMed]
Adams DL, Horton JC. Capricious expression of cortical columns in the primate brain. Nat Neurosci. 2003;6:113–114. [CrossRef] [PubMed]
Figure 1.
 
An illustration of the method of scanning the optical density of the COR over the width of the ODC. Top: the scan path (rectangles) was 10 pixels wide and orthogonal to the long axis of the columns and selected to minimize inclusion of the many blood vessels. Bottom: the average profile of 10 scans each over the CO-dark and CO-pale ODC of the normal monkey cortex (PT) aligned for comparison of the relative widths. Note that the columns are of the same average width estimated by the perpendicular line drawn from the half-amplitude density transition from the dark to the pale columns.
Figure 1.
 
An illustration of the method of scanning the optical density of the COR over the width of the ODC. Top: the scan path (rectangles) was 10 pixels wide and orthogonal to the long axis of the columns and selected to minimize inclusion of the many blood vessels. Bottom: the average profile of 10 scans each over the CO-dark and CO-pale ODC of the normal monkey cortex (PT) aligned for comparison of the relative widths. Note that the columns are of the same average width estimated by the perpendicular line drawn from the half-amplitude density transition from the dark to the pale columns.
Figure 2.
 
Samples of layer 4C ODC patterns from the six experimental monkeys. Insets: the cortical location from which the ODC example was drawn, as well as where the scan profiles of Figure 3 were made. Example of ODCs for monkeys (A) HIG, (B) HT1, (C) MIK, (D) ELL, (E) DAR, and (F) TRX. The magnification of these images is unspecified and different between panels. The panel order in Figures 2 and 3 are the same.
Figure 2.
 
Samples of layer 4C ODC patterns from the six experimental monkeys. Insets: the cortical location from which the ODC example was drawn, as well as where the scan profiles of Figure 3 were made. Example of ODCs for monkeys (A) HIG, (B) HT1, (C) MIK, (D) ELL, (E) DAR, and (F) TRX. The magnification of these images is unspecified and different between panels. The panel order in Figures 2 and 3 are the same.
Figure 3.
 
Average COR profiles from which the relative ODC widths were estimated for the six experimental monkeys. Each graph shows the average density profile for 10 CO-dark (normal eye) and companion CO-pale (experimental eye) columns. The profiles have been normalized in the x-axis for the column centers, with no adjustment in the y-axis dimension. The ratio of widths, estimated from the half-amplitude transition between the CO-dark and CO-pale columns shows the ODC associated with the experimental eye to be narrower than that of the ODC for the normal companion eye. Monkeys (A) HIG, −3-D blur, 27% loss in relative ODC width; (B) HT1, −3-D blur, 32% loss in relative ODC width; (C) MIK, −10-D blur, 53% loss in relative ODC width; (D) ELL, −10-D blur, 62% reduction in relative ODC width; (E) DAR, surgical esotropia at 3 weeks, 58% reduction in relative ODC width; and (F) TRX, surgical esotropia at 6 months, 40% reduction in relative ODC width.
Figure 3.
 
Average COR profiles from which the relative ODC widths were estimated for the six experimental monkeys. Each graph shows the average density profile for 10 CO-dark (normal eye) and companion CO-pale (experimental eye) columns. The profiles have been normalized in the x-axis for the column centers, with no adjustment in the y-axis dimension. The ratio of widths, estimated from the half-amplitude transition between the CO-dark and CO-pale columns shows the ODC associated with the experimental eye to be narrower than that of the ODC for the normal companion eye. Monkeys (A) HIG, −3-D blur, 27% loss in relative ODC width; (B) HT1, −3-D blur, 32% loss in relative ODC width; (C) MIK, −10-D blur, 53% loss in relative ODC width; (D) ELL, −10-D blur, 62% reduction in relative ODC width; (E) DAR, surgical esotropia at 3 weeks, 58% reduction in relative ODC width; and (F) TRX, surgical esotropia at 6 months, 40% reduction in relative ODC width.
Figure 4.
 
CS functions (CSFs) for the normal monkey (PT; A) and for four of the experimental monkeys. (A) The monocular CSFs of the left and right eyes of the normal monkey are indicated by the square and circle data points, whereas the diamond data points (A) represent the binocular CSF, showing the superior sensitivity of binocular summation. (B) CSFs for monkey HT1, subjected to −3-D blur that induced only a modest reduction in peak sensitivity. (C) Monocular blur of −10 D in MIK induced a severe reduction in CSF at all spatial frequencies. (D) Monocular blur of −10 D in monkey ELL had the same effect as in (C). (E) CSFs are normal and virtually identical for the two eyes in strabismus monkey TRX.
Figure 4.
 
CS functions (CSFs) for the normal monkey (PT; A) and for four of the experimental monkeys. (A) The monocular CSFs of the left and right eyes of the normal monkey are indicated by the square and circle data points, whereas the diamond data points (A) represent the binocular CSF, showing the superior sensitivity of binocular summation. (B) CSFs for monkey HT1, subjected to −3-D blur that induced only a modest reduction in peak sensitivity. (C) Monocular blur of −10 D in MIK induced a severe reduction in CSF at all spatial frequencies. (D) Monocular blur of −10 D in monkey ELL had the same effect as in (C). (E) CSFs are normal and virtually identical for the two eyes in strabismus monkey TRX.
Table 1.
 
Summary of the Individual Animal Treatments
Table 1.
 
Summary of the Individual Animal Treatments
Monkey Treatment Beginning Age of Treatment (d) Ending Age of Treatment (d)
DAR Surgical esotropia 30
TRX Surgical esotropia 182
ELL −10-D lens 14 134
MIK −10-D lens 28 88
HT1 −3-D lens 21 133
HIG −3-D lens 14 74
PT Normal control
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×