Nerve growth factor-induced ocular dominance plasticity in adult cat visual cortex.

Activity-dependent modifiability of cortical ocular dominance occurs only during early postnatal life, within the so-called "critical period," but not thereafter in adult visual cortex. To examine the role of neurotrophins in the activity- and age-dependent stimulation-induced modifiability of visual cortex, we tested whether intracortical infusion of nerve growth factor could induce ocular dominance plasticity in adult visual cortex. Nerve growth factor was continuously infused, by means of osmotic minipumps, into striate cortex of adult cats for 2 weeks. At the time of minipump implantation, one eyelid of the experimental animals was sutured closed. After 3 weeks of monocular deprivation, the ocular dominance distribution of neurons in the striate cortex was assessed using single unit recording. We found that monocular deprivation imposed on adult animals in conjunction with nerve growth factor infusion causes an ocular dominance shift toward the deprived eye. Although the underlying mechanisms remain uncertain, the results indicate that nerve growth factor can enhance activity-dependent synaptic modification and remodeling in adult visual cortex.     

Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat.

We investigated whether the transplant of Schwann cells prevents the physiological and morphological effects of monocular deprivation in the rat. On the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days, at the end of the critical period for the visual system development, we analyzed the functional properties of visual cortical neurons. Spontaneous discharge, orientation selectivity, and receptive field size of visual cortical neurons in transplanted animals were in the normal range. Transplantation of Schwann cells prevented the detrimental effects of monocular deprivation on ocular dominance and binocularity of cortical neurons. Visual acuity of the deprived eye estimated by visually evoked potentials was also normal. Schwann cells derived from adult animals were as effective as those derived from neonates. The effects of Schwann cells on monocular deprivation were dependent upon the number of cells present in the transplant so that 10(6) Schwann cells were sufficient to prevent the effect of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells. In rats transplanted with hybridoma cells producing an antibody that functionally blocks nerve growth factor (NGF), we found that the effect of cotransplanted Schwann cells on monocular deprivation was partly counteracted. We conclude that transplantation of Schwann cells prevents both functional and anatomical effects of monocular deprivation, presumably acting through the production of NGF. We propose that transplants of Schwann cells could be a promising technique for clinical applications.     

Rapid experience-dependent plasticity of synapse function and structure in ferret visual cortex in vivo

The rules by which visual experience influences neuronal responses and structure in the developing brain are not well understood. To elucidate the relationship between rapid functional changes and dendritic spine remodeling in vivo, we carried out chronic imaging experiments that tracked visual responses and dendritic spines in the ferret visual cortex following brief periods of monocular deprivation. Functional changes, which were largely driven by loss of deprived eye responses, were tightly regulated with structural changes at the level of dendritic spines, and occurred very rapidly (on a timescale of hours). The magnitude of functional changes was correlated with the magnitude of structural changes across the cortex, and both these features reversed when the deprived eye was reopened. A global rule governed how the responses to the two eyes or changes in spines were altered by monocular deprivation: the changes occurred irrespective of regional ocular dominance preference and were independently mediated by each eye, and the loss or gain of responses/spines occurred as a constant proportion of predeprivation drive by the deprived or nondeprived eye, respectively.     

The Nursing Home Minimum Data Set for Vision and Its Association with Visual Acuity and Contrast Sensitivity

OBJECTIVES: To evaluate the association between the Minimum Data Set's (MDS) Vision Patterns section and near and distance visual acuity and contrast sensitivity in nursing home residents.
DESIGN: Cross-sectional study.
SETTING: Seventeen nursing homes in the Birmingham, Alabama, area.
PARTICIPANTS: Three hundred seventy-one nursing home residents aged 55 and older with Mini-Mental State Examination scores of 13 or greater.
MEASUREMENTS: The MDS 2.0 assessment for vision from the date closest to acuity and contrast sensitivity assessment were obtained from the resident's medical record. Acuity and contrast sensitivity were measured using the ETDRS chart and Pelli-Robson chart, respectively.
RESULTS: The MDS rating of visual status was associated with distance and near visual acuity and contrast sensitivity. The MDS performed poorly in distinguishing residents with mild visual impairment from those with moderate visual impairment. For residents who were rated on the MDS as having adequate vision, 45.9% had distance acuity worse than 20/40 in the better eye, 72.8% had near acuity worse than 20/40 in the better eye, and 85.8% had contrast sensitivity less than 1.50.
CONCLUSION: The MDS 2.0 assessment for vision in nursing home residents is positively associated with visual acuity and contrast sensitivity but does not adequately distinguish between individuals with mild and moderate visual impairment and classifies many as having adequate vision who have visual impairment. The validity of the MDS 2.0 as a mechanism for triggering comprehensive eye care for nursing home residents is questionable.     

Visual performance in behaving cats after prenatal unilateral enucleation.

Prenatal unilateral enucleation in mammals causes an extensive anatomical reorganization of visual pathways. The remaining eye innervates the entire extent of visual subcortical and cortical areas. Electrophysiological recordings have shown that the retino-geniculate connections are retinotopically organized and geniculate neurones have normal receptive field properties. In area 17 all neurons respond to stimulation of the remaining eye and retinotopy, orientation columns, and direction selectivity are maintained. The only detectable change is a reduction in receptive field size. Are these changes reflected in the visual behavior? We studied visual performance in cats unilaterally enucleated 3 weeks before birth (gestational age at enucleation, 39-42 days). We tested behaviorally the development of visual acuity and, in the adult, the extension of the visual field and the contrast sensitivity. We found no difference between prenatal monocularly enucleated cats and controls in their ability to orient to targets in different positions of the visual field or in their visual acuity (at any age). The major difference between enucleated and control animals was in contrast sensitivity:prenatal enucleated cats present a loss in sensitivity for gratings of low spatial frequency (below 0.5 cycle per degree) as well as a slight increase in sensitivity at middle frequencies. We conclude that prenatal unilateral enucleation causes a selective change in the spatial performance of the remaining eye. We suggest that this change is the result of a reduction in the number of neurones with large receptive fields, possibly due to a severe impairment of the Y system.     

Changes in protein synthesis underlying functional plasticity in immature monkey visual system

Local rates of cerebral protein synthesis were determined in newborn rhesus monkeys subjected to either acute or chronic monocular visual deprivation. Chronic monocular deprivation resulted in decreased rates of protein synthesis in the laminae of the lateral geniculate nuclei innervated by the deprived eye whereas rates of protein synthesis were normal in geniculate laminae innervated by the functioning eye. Acute monocular deprivation produced no differential changes in rates of protein synthesis in any of the geniculate laminae.     

Effects of binocular deprivation on the development of clustered horizontal connections in cat striate cortex.

Intrinsic horizontal axon collaterals in the striate cortex of adult cats specifically link columns having the same preferred orientation; consequently, retrograde tracer injections result in intrinsic labeling that is sharply clustered. We have previously shown that the normal development of this circuitry involves the emergence of crude clusters from an unclustered pattern during the second postnatal week. Crude clusters are later refined to the adult level of specificity by the selective rearrangement of axonal arbors that initially project to incorrect orientation columns. Here we report that depriving animals of patterned visual experience by binocular lid suture prior to natural eye opening had no discernible effect on the emergence of crude clusters. In contrast, cluster refinement was dramatically affected by binocular deprivation. Injections of retrograde tracers in the striate cortex of animals binocularly deprived for greater than 1 month revealed only crude clusters, indicating that horizontal axon collaterals projecting to incorrect orientation columns were retained well past the age when they normally would have been eliminated. Layer 2/3 pyramidal cells from 6-week-old binocularly deprived animals had abnormal distributions of intrinsic horizontal axon collaterals that mirrored the lack of cluster refinement. The radial clustering of their horizontal collaterals was considerably less precise than normal. These cells, nevertheless, developed many of the features of normal mature arbors, including the distal axonal branches not seen in arbors from younger animals with normal visual experience. Together, these results indicate that axonal rearrangements occurred, but with reduced specificity. Thus, binocular deprivation did not simply arrest the development of this orientation-specific circuit at an immature state but limited the accuracy with which axon collaterals were added or eliminated. We suggest that development of this orientation-specific circuitry, like ocular dominance column segregation, may depend on temporal correlation of activity for regulation of axonal rearrangement. The specificity of rearrangement may be degraded in binocularly deprived cats because they do not experience sharply oriented visual stimuli necessary for concurrent activation of same-orientation columns.     

Binocular competition in the control of geniculate cell size depends upon visual cortical N-methyl-D-aspartate receptor activation.

The lateral geniculate nucleus relays visual information from the retina to cortex. One well-known anatomical consequence of monocular deprivation during early postnatal development is a shrinkage of neurons in the lamina of the lateral geniculate nucleus that receive input from the deprived eye. This is thought to reflect the competition of afferents subserving the two eyes, possibly at the level of the visual cortex. We find that blockade of N-methyl-D-aspartate receptors in kitten visual cortex disrupts this process of binocular competition. These data provide direct evidence that postsynaptic activation of cortical neurons is required for competitive changes in lateral geniculate cell size and suggest a role for N-methyl-D-aspartate receptors in anatomical as well as physiological plasticity in the mammalian visual system.     

Visual acuity and contrast sensitivity in relation to falls in an elderly population.

Visual acuity and contrast sensitivity were measured in 95 residents of a hostel for the aged (mean age = 83 years) using a dual-contrast letter chart and the Melbourne Edge Test (MET). Vision (as measured by visual acuity, the MET, low-contrast visual acuity, and difference between high- and low-contrast acuity) decreased significantly with age and all four measures were significantly correlated. Subjects with a clinical eye disorder had poorer vision than those without a disorder although the differences were not significant. Visual acuity and contrast sensitivity were not associated with body sway when subjects were standing on a firm base. However, when the subjects were placed in a situation which provided reduced support (standing on a compliant surface), body sway was associated with poor visual acuity and contrast sensitivity. There was also a difference in contrast sensitivity between those who fell one or more times in a year of follow-up and those who did not fall. It appears that reduced vision may be a predisposing factor to postural imbalance and falls in elderly persons.     

Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study

To study the incidence of clinical and subclinical optic nerve toxicity with ethambutol therapy in patients with tuberculosis and to evaluate the reversibility of its side effects after cessation of therapy. This prospective randomized controlled study included 60 newly diagnosed adult cases of tuberculosis, who were randomly assigned into two groups. The study group included 30 patients (60eyes) who received ethambutol as a part of their anti-tubercular treatment and the control group included 30 patients (60eyes) who did not receive ethambutol. The patients were examined on monthly basis. The visual parameters studied were best corrected visual acuity, pupillary reactions, optic disc changes, color vision, contrast sensitivity, pupil cycle time, visual field charting and visual evoked potential. Ethambutol was stopped in those patients in whom toxicity was detected and they were followed more frequently. Only one patient (3.3%) showed decrease in visual acuity, three patients (10%) developed visual field defects, two patients (6.7%) showed deterioration of contrast sensitivity, the pupil cycle time was prolonged in one eye and two patients (6.7%) showed abnormal visual evoked potential. During the therapy, all patients in the study group had normal pupillary reactions, fundus picture and color vision. Conclusions: Ethambutol induced ocular toxicity was seen in three patients (10%) in our study. The maximum visual recovery occurred in first six to eight weeks after stopping ethambutol. The visual recovery was complete in only one patient, but it was partial in two patients i.e. visual fields, contrast sensitivity and visual evoked potential remained abnormal.     

Labile nature of the visual recovery promoted by reverse occlusion in monocularly deprived kittens.

Kittens were monocularly deprived by closing one eye at the time of natural eye opening for periods that ranged from 4 to 14 weeks. This eye was then opened, and the other eye was closed for an approximately equal period of time. During this period of reverse occlusion, the vision of the initially deprived eye improved from apparent blindness to a level of good visual acuity. Surprisingly, however, this recovery was largely eliminated in only 2 weeks once the initially nondeprived eye was opened to restore visual input to both eyes. This finding has important implications for the nature of the mechanism(s) responsible for the dramatic physiological effects of monocular occlusion on the visual cortex. It may also help to elucidate recent observations on patching therapy in human amblyopia.     

Global impairment and therapeutic restoration of visual plasticity mechanisms after a localized cortical stroke

We tested the influence of a photothrombotic lesion in somatosensory cortex on plasticity in the mouse visual system and the efficacy of anti-inflammatory treatment to rescue compromised learning. To challenge plasticity mechanisms, we induced monocular deprivation (MD) in 3-mo-old mice. In control animals, MD induced an increase of visual acuity of the open eye and an ocular dominance (OD) shift towards this eye. In contrast, after photothrombosis, there was neither an enhancement of visual acuity nor an OD-shift. However, OD-plasticity was present in the hemisphere contralateral to the lesion. Anti-inflammatory treatment restored sensory learning but not OD-plasticity, as did a 2-wk delay between photothrombosis and MD. We conclude that (i) both sensory learning and cortical plasticity are compromised in the surround of a cortical lesion; (ii) transient inflammation is responsible for impaired sensory learning, suggesting anti-inflammatory treatment as a useful adjuvant therapy to support rehabilitation following stroke; and (iii) OD-plasticity cannot be conceptualized solely as a local process because nonlocal influences are more important than previously assumed.     

Experience-dependent regulation of CaMKII activity within single visual cortex synapses in vivo

Unbalanced visual input during development induces persistent alterations in the function and structure of visual cortical neurons. The molecular mechanisms that drive activity-dependent changes await direct visualization of underlying signals at individual synapses in vivo. By using a genetically engineered Förster resonance energy transfer (FRET) probe for the detection of CaMKII activity, and two-photon imaging of single synapses within identified functional domains, we have revealed unexpected and differential mechanisms in specific subsets of synapses in vivo. Brief monocular deprivation leads to activation of CaMKII in most synapses of layer 2/3 pyramidal cells within deprived eye domains, despite reduced visual drive, but not in nondeprived eye domains. Synapses that are eliminated in deprived eye domains have low basal CaMKII activity, implying a protective role for activated CaMKII against synapse elimination.     

Spatial visual contrast sensitivity in liver transplanted Portuguese familial amyloidotic polyneuropathy (ATTR V30M) patients

Liver transplanted patients with familial amyloidosis (FAP) patients develop earlier presbyopia due to the deposition of amyloid on the anterior capsule of the lens. Despite normal visual acuity of 20/20 Snellen chart, some patients reported complaints of impaired vision. The aim of this study is to investigate the visual spatial contrast sensitivity in these patients. This is a retrospective, nonrandomized study. Spatial contrast sensitivity was performed in both eyes of 25 FAP patients with best correct visual acuity of 20/20 Snellen chart. In each patient, one eye had visible opacification of anterior capsule of the lens. FAP patients had poorer visual contrast sensitivity than normal even in absence of visible opacification of the anterior capsule of the lens. Comparing eyes with visible opacification of anterior capsule of the lens with eyes without visible opacification of the anterior capsule of the lens, a worse visual sensitivity was observed at all frequencies tested. This occurred with similar lacrimal function in both groups. The eyes of FAP patients have decreased spatial contrast sensitivity which is worse in presence of visible opacification of the anterior capsule of the lens. This could explain the visual complaints in presence of normal visual acuity by Snellen chart.     

Visual risk factors for falls in older people

OBJECTIVES: To determine the tests most predictive of falls in community-dwelling older people from a range of visual screening tests (high and low contrast visual acuity, edge contrast sensitivity, depth perception, and visual field size). To determine whether one or more of these visual measures, in association with measures of sensation, strength, reaction time, and balance, can accurately predict falls in this group. DESIGN: Prospective cohort study of 12 months duration. SETTING: Falls and Balance Laboratory, Prince of Wales Medical Research Institute. PARTICIPANTS: 156 community-dwelling men and women age 63 to 90 (mean age 76.5, standard deviation = 5.1). MEASUREMENTS: Screening tests of vision, sensation, strength, reaction time and balance, falls. RESULTS: Of the 148 subjects available at follow-up, 64 (43.2%) reported falling, with 32 (21.7%) reporting multiple falls. Multiple fallers had decreased vision, as indicated by all visual tests, with impaired depth perception, contrast sensitivity, and low-contrast visual acuity being the strongest risk factors. Subjects with good vision in both eyes had the lowest rate of falls, whereas those with good vision in one eye and only moderate or poor vision in the other eye had elevated falling rates-equivalent to those with moderate or poor vision in both eyes. Discriminant analysis revealed that impaired depth perception, slow reaction time, and increased body sway on a compliant surface were significantly and independently associated with falls. These variables correctly classified 76% of the cases, with similar sensitivity and specificity. CONCLUSION: The study findings indicate that impaired vision is an important and independent risk factor for falls. Adequate depth perception and distant-edge-contrast sensitivity, in particular, appear to be important for maintaining balance and detecting and avoiding hazards in the environment.     

Effects of monocular deprivation on the lateral geniculate nucleus in a primate.

In many mammalian species, rearing with one eyelid closed produces a loss of vision in the deprived eye and a change in cell size in the lateral geniculate nucleus (LGN). In cats, the reduction in the size of deprived LGN cells has been correlated with a loss of one functional class of cells, Y cells. In primates, such as galago, LGN cells also exhibit marked changes in size with deprivation. In the present study we recorded from single cells in the LGN of monocularly deprived galagos to determine if such changes in cell size would be accompanied by changes in physiological properties. The results revealed no alterations in the distribution or functional properties of any cell class. The differences in the effects of monocular deprivation on the function of LGN cells in cats and primates are most easily explained by a fundamental difference in visual system anatomy. In cats, different classes of retinal afferents (X vs. Y) are in a position to compete for postsynaptic LGN neurons: in primates, segregation of cell classes into different layers may preclude such developmental interactions.     

Initial recovery of vision after early monocular deprivation in kittens is faster when both eyes are open

A comparison was made of the speed of visual recovery in the deprived eye of kittens after a 6-day period of monocular deprivation imposed at 5-9 weeks of age in two postdeprivation conditions. In one condition, binocular recovery (BR), both eyes were open, whereas in the other condition, reverse lid-suture (RLS), the formerly nondeprived eye was closed to force the animal to use the originally deprived eye. In littermate pairs, BR kittens began to recover form vision 12 to 30 h before those subjected to RLS. The vision of the deprived eye of the BR animals remained superior to that of their RLS littermates for 4-8 days. Although this finding is difficult to reconcile with competitive mechanisms of synaptic plasticity, it supports a prediction of an alternative model of synaptic plasticity [Bienenstock, E. L., Cooper, L. N. & Munro, P. W. (1982) J. Neurosci. 2, 32-48] for slower initial recovery with RLS because of the time required to reset the modification threshold.     

Adrenal splanchnic innervation modulates adrenal cortical responses to dehydration stress in rats

Classically, the production of glucocorticoids by the adrenal gland is thought to be controlled exclusively by adrenocorticotropic hormone (ACTH). However, there are several examples in stressed humans and animals of increased plasma glucocorticoids in the absence of increased plasma ACTH, suggesting that an additional, non-ACTH mechanism(s) may contribute to the control of glucocorticoid production. The present studies were designed to determine the role of the thoracic splanchnic nerve in controlling plasma corticosterone levels in response to chronic water deprivation in rats, a model previously reported to demonstrate dissociations between plasma corticosterone and ACTH. Briefly, rats underwent right unilateral adrenalectomy and left thoracic splanchnic nerve transection or sham transection. After recovery, rats were water deprived for 48 h or given free access to water, and then sacrificed for collection of plasma and adrenal glands. Water deprivation resulted in consistent, robust increases in plasma corticosterone that were attenuated by splanchnic nerve transection, in the absence of changes in post-dehydration plasma ACTH. Adrenal content of steroidogenic acute regulatory factor (StAR) and cyclic AMP (cAMP) were increased after dehydration; splanchnic nerve transection decreased post-dehydration adrenal cAMP, but not StAR. Splanchnic nerve transection also attenuated plasma corticosterone responses to submaximal doses of ACTH in dexamethasone-blocked, dehydrated rats, suggesting a decreased adrenal sensitivity to ACTH. Collectively, the present results demonstrate that the thoracic splanchnic nerve normally augments the adrenal corticosterone response to dehydration stress by increasing adrenal sensitivity to ACTH, and this augmentation is associated with elevations in adrenal cAMP content. These data support the hypothesis that the splanchnic innervation of the adrenal gland represents an additional physiological mechanism to control stress-induced adrenal cortical responses in vivo.     

The objective assessment of visual contrast sensitivity by pattern reversal visual evoked potentials in diabetes

Recent studies have described abnormalities of visual evoked potentials and pattern electroretinography in diabetics without retinopathy. The visual contrast sensitivity, determined by psychophysical tests, has proved to be abnormal in diabetic patients with and without clinical retinopathy. In this study we evaluated contrast sensitivity function using both electrophysiologic and psychophysical methods. The objective assessment of functional visual contrast sensitivity was superior to psychophysical evaluation in the detection of contrast sensitivity alterations. No relationships were found between contrast sensitivity dysfunction and abnormalities of pattern electroretinography or fluorescein angiography. Our data suggest that functional visual deficits might precede background retinopathy and that the involvement of foveal function is early and very frequent in diabetic patients, even if they have normal visual acuity.