M.L.J. Crawford

Visual field defects and neural losses from experimental glaucoma

Glaucoma is a relatively common disease in which the death of retinal ganglion cells causes a progressive loss of sight, often leading to blindness. Typically, the degree of a patients visual dysfunction is assessed by clinical perimetry, involving subjective measurements of light-sense thresholds across the visual field, but the relationship between visual and neural losses is inexact. Therefore, to better understand of the effects of glaucoma on the visual system, a series of investigations involving psychophysics, electrophysiology, anatomy, and histochemistry were conducted on experimental glaucoma in monkeys. The principal results of the studies showed that, (1) the depth of visual defects with standard clinical perimetry are predicted by a loss of probability summation among retinal detection mechanisms, (2) glaucomatous optic atrophy causes a non-selective reduction of metabolism of neurons in the afferent visual pathway, and (3) objective electrophysiological methods can be as sensitive as standard clinical perimetry in assessing the neural losses from glaucoma. These experimental findings from glaucoma in monkeys provide fundamental data that should be applicable to improving methods for assessing glaucomatous optic neuropathy in patients.

Behavioral studies on the effect of abnormal early visual experience in monkeys: Spatial modulation sensitivity

Spatial modulation sensitivity functions have been investigated by behavioral methods in two monkeys reared with normal visual experience and 12 monkeys reared with abnormal, early visual experience. Experimental treatments were initiated when the animals were approximately one month of age. Two monkeys were each treated with one of the following procedures: (1) long-term monocular lid suture, (2) short-term monocular lid suture, (3) surgically induced esotropia, (4) surgically induced exotropia, (5) optical dissociation of binocular vision with ophthalmic prisms, or (6) chronic monocular cycloplegia. The results of the studies showed a severe loss of contrast sensitivity of the treated eyes compared to the control eyes for monkeys reared with monocular lid suture or surgically induced esotropia. Surgically induced exotropia resulted in a moderate reduction in sensitivity of the deviated eye while optical dissociation resulted in a mild reduction in sensitivity of one eye compared to the other. One of the two monkeys reared for seven months with chronic monocular cycloplegia had a relative reduction in contrast sensitivity of the treated eye, but the other monkey had equal sensitivities in the two eyes. However, binocular summation experiments showed that even though the relative difference between the monocular sensitivities was small or absent for the monkeys reared with optical dissociation or chronic monocular cycloplegia, none of them demonstrated binocular vision in these experiments.

Behavioral studies of stimulus deprivation amblyopia in monkeys.

Abstract Contrast sensitivity and increment-threshold functions were studied for three rhesus monkeys with stimulus deprivation amblyopia. The monkeys right eyelids were sutured closed before the age of 1 month for periods of two weeks, 19 months and 23 months. Contrast sensitivity measurements for all three monkeys showed greatly reduced visual function in the deprived eye with a high spatial frequency cut-off 6 octaves lower in the deprived than the nondeprived eyes. The increment-threshold data collected for the two long-term lid-sutured monkeys showed both photopic and scotopic abnormalities in the deprived eyes. For example, with complete dark adaptation although the spectral sensitivity data for both the deprived and nondeprived eyes were well fit by the scotopic luminosity function, the sensitivity for the deprived eye was approximately 4 log units lower than the nondeprived eye. In addition, the spectral sensitivity data for the deprived eyes showed scotopic luminosity functions for achromatic adapting field luminances of 188, 750 and 3000 td whereas the nondeprived eye showed normal photopic function for all light adapted conditions. Even when the spectral sensitivity measurements were made in the presence of intense blue backgrounds, the data obtained for the deprived eyes were best described as showing scotopic function over the short wavelengths and photopic function only at the longer wavelengths. The increment-threshold functions for achromatic stimuli showed normal rod-cone interactions in the nondeprived eyes, but the functions were monotonic for the deprived eyes over a 9 log unit range of background luminances. Therefore, the results of these experiments show that stimulus deprivation causes profound defects for visual resolution, rod saturation and the rate of change of sensitivity with light adaptation.

Contribution of the retinal ON channels to scotopic and photopic spectral sensitivity

Visual information encoded by the middle-wavelength-sensitive (MWS) and long-wavelength-sensitive (LWS) cones in the primate retina are processed by both depolarizing (ON) and hyperpolarizing (OFF) bipolar cells. In contrast, signals from the short-wavelength-sensitive (SWS) cones and dark-adapted rod photoreceptors are thought to be carried almost exclusively by ON bipolar cells (Gouras & Evers, 1985). Consequently, it would be expected that functional inactivation of the retinal ON channels at the bipolar cell level would produce selective deficits in visual functions mediated by rods and SWS cones. We have examined this hypothesis by injecting rhesus monkeys with 2-amino-4-phosphonobutyric acid (APB), a pharmacological agent that reduces the responsiveness of retinal ON neurons, and psychophysically measuring the changes in spectral sensitivities. Under adaptation conditions that isolated rod function, APB caused, as expected, a substantial loss in rod-mediated spectral sensitivity. However, under photopic conditions, cone-mediated spectral sensitivity, including that associated with the SWS cones, was relatively unaffected. These results demonstrate distinct organizational differences between the rod and cone systems; specifically, they indicate that the rod system is more dependent upon retinal ON channels than the cone system. Our failure to find a selective visual deficit related to SWS cone function under photopic viewing conditions suggests that the OFF system can mediate stimulus detection throughout the visible spectrum and that the ability of the OFF system to process signals from the SWS cones has been underestimated.

Loss of stereopsis in monkeys following prismatic binocular dissociation during infancy

Prismatic binocular dissociation was used during infancy to mimic conditions of strabismus in macaque infants. Prisms worn continuously produce a diplopia unfavorable for the maintenance and development of the binocular visual system. Prism-reared monkeys were tested as young adults and found to be permanently stereoblind for dynamic random dot stereograms. Control monkeys did comparably to humans on such tests. It is concluded that short periods of diplopia attendant with strabismus are sufficient to produce permanent stereoblindness.

The effects of reverse monocular deprivation in monkeys II. Electrophysiological and anatomical studies

SummaryMonkeys had one eye closed at about 30 days of age for 14, 30, 60, or 90 days, then opened, and the fellow eye closed for another 120 days. The animals then had at least 10 months of binocular visual experience before extensive behavioral training and testing were carried out. In terminal experiments concluded more than 18 months later, microelectrode investigations of the striate cortex demonstrated that there was almost a complete absence of binocular neurons in all animals. The initially deprived eyes (IDEs) dominated the majority of cortical neurons, even when soma size measurements of lateral geniculate neurons indicated that the LGN cells driven by the IDE had not regained their normal size. The monkeys which had significant interocular differences in spatial vision also exhibited abnormalities in the distribution of the metabolic enzyme, cytochrome oxidase (CO), within the striate cortex. These results demonstrate that many of the severe alterations in cortical physiology and eye dominance produced by early monocular form deprivation can be reversed, with recovery of normal cortical function, via the reverse-deprivation procedure.

Ocular dominance, eye alignment and visual acuity in kittens reared with an optically induced squint

A horizontal concomitant strabismus produced optically in kittens with prisms caused a decrease in the proportion of binocularly excitable striate neurons with approximately equal percentages of neurons being driven by each eye. In addition, preventing fusion with prisms resulted in alterations in interocular alignment and in some cases a mild strabismic amblyopia. The changes in ocular dominance were dependent on the amount and direction of the prism induced deviation; however, regardless of the type of prisms worn, the kittens which demonstrated interocular misalignments were esotropic.

Optical control of early visual experience in monkeys

Experimental control of the early visual experience of primates has employed a variety of surgical manipulations such as suturing the eyelids or cutting the extraocular muscles in order to mimic infantile visual disorders of children. For several years, we have successfully used optical means for these experimental simulations and the methods are described here.

Keeping an eye on the brain: the role of visual experience in monkeys and children

The quality of visual experience during infancy determines the functional sensitivity and precision of the mature primate visual system. Infant monkeys subjected to monocular form deprivation show a period of critical visual development that, though decreasing in sensitivity, lasts throughout the first 2 years of life. Photopic threshold spectral sensitivity appears to have a briefer critical period, which is essentially complete by 6 months old, whereas scotopic visual functions appear well developed by 3 months old. Binocular visual functions seem to have the longest period of sensitivity to abnormal visual experience because periods of monocular form deprivation initiated during the first 2 years affect visual functions. Viewing the world through prisms, which mimics the condition of strabismus, causes a permanent loss of cortical binocular cells and stereopsis in monkeys. This result explains stereoblindness in children having equivalent clinical histories.

Column spacing in normal and visually deprived monkeys

Abstractu2002A recent model for the development of the pattern of eye-dominance domains in primary visual cortex predicts that stimulus conditions during early visual life determine the spacing (or periodicity) of ocular dominance columns (ODC). The model predicts that normal binocular visual experience consists of highly correlated binocular stimulation and leads to relatively narrow ODC spacing, while abnormal binocular visual stimulation attendant with strabismus consists of non-correlated, incoherent, and asynchronous stimulation and leads to wider than normal ODC spacing. Evidence in support of the model has been presented for strabismus in the kitten. We tested the predictions of the model in normal monkeys and others subjected to various forms of abnormal visual experience during infancy. We identified and measured the inter-column spacing (or periodicity) in the V1 cortex of 19 adult monkeys (M. mulatta) using the cytochrome-oxidase (CO) histochemical method. There were no significant differences in the V1 inter-column spacing between normal adult monkeys (n=5) and other adult monkeys having had monocular-form deprivation (n=5), experimental anisometropia (n=5), or experimental strabismus (n=4) early in life. The quality of early binocular visual experience is not a significant determinant of the inter-column spacing in primate V1 cortex. Therefore, the model predicting an increase in the ODC periodicity with strabismus is not supported.