Biomedical subjects

M L Crawford

Publications and source records attributed to M L Crawford.

At least 37 records · Page 2Linked to original sources

PubMed1995

Spectacle lenses alter eye growth and the refractive status of young monkeys.

The influence of visual experience on ocular development in higher primates is not well understood. To investigate the possible role of defocus in regulating ocular growth, spectacle lenses were used to optically simulate refractive anomalies in young monkeys (for example, myopia or nearsightedness). Both positive and negative lenses produced compensating ocular growth that reduced the lens-induced refractive errors and, at least for low lens powers, minimized any refractive-error differences between the two eyes. These results indicate that the developing primate visual system can detect the presence of refractive anomalies and alter each eye's growth to eliminate these refractive errors. Moreover, these results support the hypothesis that spectacle lenses can alter eye development in young children.

Accommodation, Ocular↗

PubMed1995

Immunoglobulin concentrations in serum in response to injectable immunoglobulin in neonatal dairy calves.

Thirty Holstein bull calves were used to investigate the use of an injectable solution of purified Ig to increase Ig in serum of neonatal calves. The Ig were from abbatoir blood purified by column chromatography. Calves were blocked by date of birth and assigned randomly to treatment within block. Treatments were s.c. injections of Ig solution (30 or 60 mg of Ig/ml) or .9% NaCl with or without colostrum (41.1 g of IgG/L) feeding. Calves were injected by 24 h of age. The mass of Ig injected was 1.05 g/kg of BW. Calves received 2 L of pooled colostrum or commercial milk replacer at 0, 12, 24, and 36 h. Blood was sampled at 0 and 48 h postinjection and at 28 d of age, and serum was analyzed for IgG and IgM by radial immunodiffusion. Mean IgG and IgM in serum of calves injected with Ig were 4.2 and .7 g/L, respectively, and were higher than in calves receiving no Ig. Mean IgG (14.6 g/L) and IgM (1.0 g/L) concentrations in serum of calves fed colostrum were higher than in other calves. Subcutaneous Ig provided moderate amounts Ig in serum.

Animal Nutritional Physiological Phenomena↗

PubMed1993

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.

Animals↗

PubMed1992

Prior binocular dissociation reduces monocular form deprivation amblyopia in monkeys.

The profound visual deficits associated with early monocular form deprivation (MD) are caused largely by competitive binocular interactions in the visual cortex. We tested the hypothesis that disrupting normal cortical binocularity prior to the onset of MD would reduce the degree of form deprivation amblyopia compared to that produced in animals that had normal binocular vision prior to MD. An optical strabismus was maintained in two rhesus monkeys between 30 and 90 d old, a rearing strategy that substantially reduces excitatory cortical binocular interactions. Subsequently, the lids of one eye were sutured closed for 9 mo. Comparison data were obtained from a series of form-deprived monkeys reared in a normal manner prior to the onset of MD. Psychophysical procedures were employed to measure the effects of the rearing procedures on the spatial contrast sensitivity functions for each eye. By itself, MD resulted in a severe amblyopia. The spatial resolution of the deprived eyes of monkeys lid sutured by 5 mo of age was about 6 octaves lower than normal values (Snellen acuities of about 20/2000). In contrast, equivalent periods of MD had a much smaller effect on the spatial vision of the prism-reared monkeys. In both cases, the deprived-eye cut-off spatial frequencies were within 1 octave of the nondeprived-eye values and were comparable to cut-offs for binocularly form-deprived monkeys. The results demonstrate that prior binocular image dissociation protects young monkeys from the effects of MD, probably by reducing the potential for antagonistic, competitive binocular interactions in the visual cortex.

Amblyopia↗

PubMed1992

The lateral geniculate nucleus in human strabismic amblyopia.

Cell shrinkage in monkey lateral geniculate nucleus (LGN) layers supplied by the amblyopic eye have been described in experimental amblyopia caused by visual deprivation, anisometropia, and strabismus. A human brain from a strabismic amblyope became available for study and the authors compared cell sizes in LGN layers receiving input from the normal and the amblyopic eye. Significant cell shrinkage was present in layers connected with the amblyopic eye, and was most evident in the ipsilateral LGN. These findings support the validity of the monkey model for the study of strabismic amblyopia by showing, for the first time, changes in the brain from a human strabismic amblyope that are similar to those previously described in monkeys.

Aged↗

PubMed1991

Functional effects of bilateral form deprivation in monkeys.

Psychophysical methods were used to study the effects of binocular form deprivation, initiated at 1 month of age, on the visual sensitivities of young monkeys. All the monkeys reared with bilateral form deprivation for 7 weeks or longer had reduced spatial contrast sensitivity for both eyes. Although the contrast sensitivity deficits of the bilaterally form-deprived monkeys generally were larger for one eye than the other, the magnitudes of the deficits were small compared with those produced by similar periods of unilateral form deprivation. For other monocular vision functions investigated, temporal contrast sensitivity and increment-threshold spectral sensitivity, the data for the bilaterally form-deprived animals showed only minor variations from those of the control monkeys. However, none of the bilaterally form-deprived monkeys had binocular vision on either measures of binocular summation or stereodetection, even if the animal had normal monocular vision functions. Therefore, these results show that monocular sensory deficits caused by abnormal early visual experience as a result of bilateral form deprivation are much less severe than those caused by unilateral form deprivation. The differences in the severity of visual deficits may be attributed to the consequences of anomalous binocular competition associated with unilateral form deprivation that was minimized during bilateral form deprivation. Thus, these results illustrate that anomalous binocular competition is more detrimental to the developing visual system of infants than direct deprivation per se.

Amblyopia↗

PubMed1991

Bilateral form deprivation in monkeys. Electrophysiologic and anatomic consequences.

The response characteristics of neurons in the striate cortex are described for rhesus monkeys that underwent bilateral form deprivation by surgical closure of the eyelids starting within the first month of life and lasting for 2, 6, 7, 13, or 16 weeks. The monkeys had been tested for visual deficits resulting from these experimental deprivations. Single-unit recordings from the striate cortices of these animals showed a single significant abnormality; the absence of excitatory binocular input. Whereas, 76% of the neurons in the foveal striate cortex of the normal animals were binocular, fewer than 20% of the neurons in the experimental monkeys were binocular. However, each eye was well represented by monocular cells. As demonstrated in oblique microelectrode penetrations, the cortical eye-dominance zones for each eye appeared to be of equal width with sharp transitions at the monocular boundaries. The sizes of the cells of the lateral geniculate nuclei were smaller (-15%) than those in controls. Binocular form deprivation early in life has its most obvious effect on the physiology and function of cortical binocular neurons and secondarily on the size of neurons of the lateral geniculate nucleus.

Animals↗

PubMed1990

Behavioral studies of the sensitive periods of development of visual functions in monkeys.

The age-dependent effects of monocular form deprivation on psychophysically determined visual functions were investigated in rhesus monkeys. Monocular form deprivation was initiated at various ages from 1 to 25 months and maintained for 18 months. The effects of form deprivation varied across the visual functions evaluated. Absolute scotopic sensitivity was depressed by form deprivation initiated only at 1 or 2 months of age. Photopic, increment-threshold spectral sensitivity functions showed alterations in sensitivity levels for monkeys treated at 5 months of age or earlier, with no effect thereafter. Monocular form deprivation at 1 to 5 months of age resulted in profound deficits in spatial modulation sensitivity. The effects on spatial vision decreased systematically as the age of onset was delayed from age 6 to 18 months. Finally, binocular summation measures revealed an absence of binocular vision even for the monkey form-deprived at 25 months of age, i.e. the experimental treatment series failed to define the upper limit of the age-range for the effects of monocular form deprivation on binocular summation mechanisms. Comparisons of the age-dependent effects of monocular form deprivation across the various functions demonstrated that the sensitive period, i.e. the period of life during which a visual function may be altered by monocular form deprivation, was different for each of the psychophysical measures of visual function.

Animals↗

PubMed1990

Characteristics of endothelin-1 and endothelin-3 stimulation of phosphoinositide breakdown differ between regions of guinea-pig and rat brain.

Endothelin-3 was almost equipotent with endothelin-1 (ET-1) in stimulating phosphoinositide hydrolysis, as indicated by [3H]inositol phosphate formation, in cross-chopped slices of guinea-pig cerebellum, rat cerebellum and rat cerebral cortex. The magnitude of [3H]inositol phosphate formation was greatest in guinea-pig cerebellum, approximately 10-fold over basal levels. The similar level of [3H]IP1 accumulation produced by 1 mumol.l-1 ET-1 in rat cerebellum and cerebral cortex (circa 3-fold over basal) did not mirror the large difference in high-affinity [125I]ET-1 binding sites in the two regions. Moreover, the EC50 for ET-induced [3H]IP1 formation differed markedly between the three tissues (7 +/- 2 nmol.l-1 in rat cerebral cortex, 65 +/- 15 nmol.l-1 in guinea-pig cerebellum and greater than 200 nmol.l-1 in rat cerebellum). Only in rat cerebral cortex was the EC50 of the same order as has been reported for peripheral responses to ET-1.

Animals↗

PubMed1990

Ca2(+)-dependence provides evidence for differing mechanisms of GABA-induced inositol phosphate formation and GABA potentiation of inositol phosphate formation induced by noradrenaline in rat cerebral cortex.

[3H]Inositol phosphate formation ([3H]IP) induced by gamma-aminobutyric acid (GABA) in slices of rat cerebral cortex prelabelled with [3H]inositol was abolished in Krebs-Henseleit medium without added Ca2+, but could be restored by addition of Ca2+. In contrast, GABA potentiation of noradrenaline-induced [3H]IP accumulation in the same tissue was still observed in the absence of added Ca2+. This provides evidence (a) that the effect of GABA alone on [3H]IP formation is indirect and (b) that the mechanism of this effect is unlikely to be the same as for the potentiation by GABA of [3H]IP accumulation induced by noradrenaline.

Animals↗

PubMed1990

Potentiation by gamma-aminobutyric acid of alpha 1-agonist-induced accumulation of inositol phosphates in slices of rat cerebral cortex.

Noradrenaline-induced accumulation of 3H-labeled inositol mono-, bis-, and trisphosphate (IP1, IP2, and IP3, respectively) in lithium-treated slices of rat cerebral cortex preincubated with [3H]inositol was potentiated by gamma-aminobutyric acid (GABA). However, the effect on [3H]IP2 accumulation was much greater than that on [3H]IP1 or [3H]IP3 accumulation. The principal effect of GABA on noradrenaline concentration-response curves for both [3H]IP1 and [3H]IP2 was to cause an increase in the maximal response attainable. However, whereas the EC50 for GABA potentiation of [3H]IP1 formation was 0.5 mM, the curve for the potentiation of [3H]IP2 formation showed a marked upturn at GABA concentrations of greater than 1 mM. Prazosin (1 microM) blocked the noradrenaline-induced formation of all three inositol phosphates (IPs), in both the presence and the absence of 2 mM GABA. 3H-IP formation induced by phenylephrine and methoxamine was also potentiated by GABA, and again the greatest effect was on [3H]IP2 accumulation. The ratio of [3H]IP2/[3H]IP1 formed in response to 100 microM noradrenaline was increased by 2 mM GABA at all times from 10 to 60 min, whereas the ratio of [3H]IP3/[3H]IP1 was little altered. The effect of GABA was not mimicked by the GABAA agonists isoguvacine and 3-aminopropanesulphonic acid and was not blocked by bicuculline methiodide. (-)-Baclofen, a GABAB agonist, did produce some stimulation of the response to noradrenaline, but to a much lesser extent than GABA. Of the agents tested, nipecotic acid came nearest to reproducing the effect of GABA, in that the major effect was on [3H]IP2 accumulation. The effects of 2 mM GABA and 2 mM nipecotic acid were not additive. GABA potentiation of noradrenaline-induced 3H-IP formation was still apparent in the absence of Li+, but the increase of [3H]IP2 content was less than that of [3H]IP1 content.

Adrenergic alpha-Agonists↗

PubMed1990

gamma-Aminobutyric acid inhibition of histamine-induced inositol phosphate formation in guinea-pig cerebellum: comparison with guinea-pig and rat cerebral cortex.

1. gamma-Aminobutyric acid (GABA), 2 mM, inhibited basal accumulation of [3H]-inositol monophosphate ([3H]-IP1) in lithium-treated slices of guinea-pig cerebellum preincubated with [3H]-inositol. In contrast, 2 mM GABA stimulated the accumulation of [3H]-IP1 in rat cerebral cortical slices over a 60 min incubation period, but had no significant effect in slices of guinea-pig cerebral cortex. The estimated IC50 for the inhibitory action of GABA in guinea-pig cerebellar slices was 0.52 +/- 0.12 mM. 2. GABA inhibited histamine-induced [3H]-IP1 accumulation in guinea-pig cerebellar slices in a non-competitive manner. The best-fit value for the maximum level of inhibition was 74 +/- 6%. The estimated IC50 for GABA was 0.77 +/- 0.15 mM and was not significantly different from the IC50 for inhibition of the basal accumulation of [3H]-IP1. The response to histamine in guinea-pig and rat cerebral cortical slices was also inhibited by 2 mM GABA. 3. In guinea-pig cerebellar slices 2 mM GABA potentiated histamine-induced [3H]-inositol bisphosphate ([3H]-IP2) accumulation, whereas in both guinea-pig and rat cerebral cortex the effect was inhibition. 4. Isoguvacine and muscimol, GABAA-selective agonists, and (-)-baclofen, GABA(B)-selective, had no significant effect on basal or histamine-stimulated accumulation of [3H]-IPs in guinea-pig cerebellar slices. (-)-Baclofen had only a weak inhibitory effect on [3H]-IP1 accumulation in guinea-pig-cerebral cortex (16 +/- 6% inhibition with 10 microM (-)-baclofen), whereas in rat cerebral cortex (-)-baclofen mimicked the inhibitory effect of GABA. 5. Nipecotic acid (1 mM) had qualitatively similar effects to those of 2mm GABA in guinea-pig cerebellar slices. 6. The competitive GABA uptake inhibitors SK&F 89976-A, SK&F 100330-A and SK&F 100561-A were potent histamine H,-receptor antagonists, as indicated by the inhibition of [3H]-mepyramine binding to homogenates of guinea-pig cerebellum and cerebral cortex. 7. GABA (2 mM) caused a small inhibition (12 + 3%) of [3H]-inositol incorporation into total inositol phospholipids in guinea-pig cerebellar slices, as in rat cerebral cortical slices, whereas 0.2mm histamine caused a small stimulation (15 + 4%). In the presence of both GABA and histamine, [3H]-inositol incorporation was unchanged from basal (101 + 5%). 8. GABA also inhibited [3H]-IP1 formation induced by endothelin-1 in guinea-pig cerebellar slices and increased, but not significantly, the amount of [3H]-IP2 accumulated. This, taken with the inhibitory effect on basal and histamine-stimulated accumulation, suggests that the action of GABA in guinea-pig cerebellar slices may be non-selective and may not be exerted through a specific GABA receptor.

Animals↗

PubMed1989

The effects of reverse monocular deprivation in monkeys. I. Psychophysical experiments.

Monkeys 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 behavioral training and testing were begun. All subjects were used in a series of psychophysical investigations during the next two years. The results of the behavioral studies indicated that the initially deprived eyes (IDE) of the two monkeys that were subjected to initial deprivation periods of 14 or 30 days recovered normal or near-normal spatial contrast sensitivity. In contrast, the two animals which underwent longer periods of initial deprivation showed incomplete recovery, especially for high spatial frequency stimuli. All of the monkeys exhibited a reduction in spatial contrast sensitivity for their reverse deprived eyes (RDE); the earlier the onset of the reverse-deprivation procedures (i.e., the shorter the initial period of deprivation), the greater the deficit in the RDE's spatial contrast sensitivity. Measurements of temporal contrast sensitivity showed that all of the subjects' IDEs had normal or near-normal sensitivity levels. However, the reverse-deprivation procedures initiated at 90 days of age or earlier produced a frequency-dependent reduction in the RDE's temporal modulation sensitivity. The measures of increment-threshold spectral sensitivity revealed that only the RDE of the monkey that had the shortest initial deprivation period had an abnormal spectral sensitivity function. The results demonstrate that many of the severe behavioral deficits produced by early monocular form deprivation can be recovered via reverse-deprivation procedures. However, depending upon the length of the initial deprivation period and the age at which the reversal procedure is initiated, the second deprivation period can also adversely affect the functional capacity of the RDE.

Animals↗

PubMed1989

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

Monkeys 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.

Animals↗

PubMed1989

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.

Aminobutyrates↗

PubMed1988

GABAB receptor-mediated inhibition of histamine H1-receptor-induced inositol phosphate formation in slices of rat cerebral cortex.

Histamine-stimulated accumulation of [3H]inositol monophosphate ([3H]IP1) in lithium-treated slices of rat cerebral cortex was inhibited by gamma-aminobutyric acid (GABA) (IC50 0.30 +/- 0.03 mM). The maximum level of inhibition was 69 +/- 2%. GABA alone caused a small stimulation of basal accumulation of [3H]IP1. The inhibitory action of GABA on the response to histamine was mimicked by the GABAB agonist (-)-baclofen, IC50 0.69 +/- 0.04 microM, which was 430-fold more potent as an inhibitor than the (+)-isomer. (-)-Baclofen also inhibited histamine-induced formation of [3H]inositol bisphosphate ([3H]IP2) and [3H] inositol trisphosphate ([3H]IP3). Inhibition curves for GABA and for (-)-and and (+)-baclofen had Hill coefficients greater than unity. (-)-Baclofen, at concentrations that caused inhibition of histamine-induced [3H]IP1 accumulation, did not alter the basal level of [3H]IP1 or the incorporation of [3H]inositol into total inositol phospholipids. Isoguvacine, a GABAA agonist, had no effect on either the histamine-stimulated or basal accumulation of [3H]IP1. GABA had no effect on carbachol-stimulated [3H]IP1 formation.

Animals↗

PubMed1987

Observations on the effects of form deprivation on the refractive status of the monkey.

The consistency of the refractive error alterations produced by monocular form deprivation in developing monkeys and the influence of the duration and the age at the onset of deprivation on the magnitude of these alterations was investigated. Refractive error and axial length measurements are presented for a group of monkeys which had one eye sutured closed for a period exceeding 18 months beginning at various ages ranging from 26 days to 25 months. In addition, we pooled and reanalyzed refractive error and axial length data for monocularly form-deprived monkeys from previous studies. When the alterations in the deprived eye's refractive status are specified with respect to the fellow nondeprived eye, the results are, with a few noteworthy exceptions, consistent between laboratories and individual animals. In most cases, early monocular form deprivation causes the treated eye to develop a longer axial length and to manifest a more myopic/less hyperopic refractive error than the fellow nontreated eye. The magnitude of this deprivation-induced alteration is generally dependent on the duration and the age at the onset of form deprivation. The earlier the deprivation is initiated and the longer it is maintained, the greater the degree of the relative myopia produced in the deprived eye.

Animals↗

PubMed1986

Multiple sensitive periods in the development of the primate visual system.

Early in life, abnormal visual experience may disrupt the developmental processes required for the maturation and maintenance of normal visual function. The effects of retinal image deprivation (monocular form deprivation) on four psychophysical functions were investigated in rhesus monkeys to determine if the sensitive period is of the same duration for all types of visual information processing. The basic spectral sensitivity functions of rods and cones have relatively short sensitive periods of development (3 and 6 months) when compared to more complex functions such as monocular spatial vision or resolution (25 months) and binocular vision (greater than 25 months). Therefore, there are multiple, partially overlapping sensitive periods of development and the sensitive period for each specific visual function is probably different.

Age Factors↗