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Biomedical subjects

D P Crewther

Publications and source records attributed to D P Crewther.

At least 19 recordsLinked to original sources
PubMed2001

Altered expression of alternatively spliced isoforms of the mRNA NMDAR1 receptor in the visual cortex of strabismic cats.

PURPOSE: Although much has been written about the role of the NMDA receptor's role in experience dependent visual plasticity, the function of the NMDAR1 receptor subunit in the post-plasticity stage of development is still not well understood. However, in the well studied model of strabismic amblyopia where binocularity is reduced, but where most primary visual cortex neurons can be driven by one or other eye, the density of expression of NMDAR1 receptor protein is significantly reduced, compared to normals. This study aims to identify which of eight isoforms of the spliced heterogeneous variants of the NMDAR1 mRNA receptor gene are associated with this decrease in expression as a means of elucidating possible function. METHODS: A series of digoxygenin-labelled oligonucleotide probes based on the human gene sequence have been used for in situ hybridization (ISH) of sections from the striate cortex of four adult cats. The probes were used to uniquely detect the expression of alternatively spliced mRNA variants in 66,487 cells from sections from the area centralis projection of two normal cats and two cats made esotropic as kittens by tenotomy at two weeks of age. RESULTS: As expected, total NMDAR1 mRNA isoform expression was significantly lower in the striate cortex of strabismic compared to normal cats. The proportion of cortical cells expressing the R1-a, R1-b, and R1-1 isoforms in strabismic animals was decreased while the proportion expressing R1-3 was increased, especially in layers V and VI. No significant difference in expression of the R1-2 and R1-4 isoforms was seen comparing strabismic and normal cats. CONCLUSIONS: These results confirm our previous findings and suggest that transcriptional inhibition of specific isoforms of NMDAR1 mRNA may underlie the change in receptor expression. This preferential reduction in the proportion of neurons bearing particular NMDAR1 isoforms, i.e. isoforms R1-a and b, and R1-1 with partial compensation through the expression of the R1-3 isoform, is more likely related to lowered proportion of binocularly activated neurons in the strabismic cat than to changes in eye dominance or the presence of amblyopia in one eye.

Alternative Splicing↗
PubMed2001

Effects of a non-steroidal (ketorolac tromethamine) and a steroidal (dexamethasone) anti-inflammatory drug on refractive state and ocular growth.

Topical steroidal anti-inflammatory drugs (SAID) and non-steroidal anti-inflammatory drugs (NSAID) are known to affect fluid balance. The effects of twice daily topical applications of Maxidex (dexamethasone, a SAID), Acular (ketorolac, a NSAID), and saline were examined biometrically on the development of refractive errors and eye growth in chicks raised from days 3-12 wearing either a monocular +10 D, 0 D, or -10 D lens. Biometric analysis showed that neither SAID nor NSAID nor saline affected refractive error compensation but that the anti-inflammatory drugs affected eye growth. In chicks reared with a +10 D lens, dexamethasone induced a decrease in axial length (AL), vitreous chamber (VC) and anterior chamber (AC) depth, while ketorolac only induced a decrease in AC. In -10 D lens chicks dexamethasone again induced a decrease in AL and VC, but did not affect AC depth, whereas ketorolac only induced an increase in AC depth. Taken together, these results suggest that anti-inflammatory drugs can induce changes in ocular size without affecting refractive state and, as such, have implications for the management of progressive myopia.

Administration, Topical↗
PubMed2001

Comparison of refractive state and circumferential morphology of retina, choroid, and sclera in chick models of experimentally induced ametropia.

PURPOSE: Simultaneous comparisons of the circumferential morphological tissue profiles and final refractions from form-deprivation myopia (FDM), defocus-induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia have been made to test the hypothesis that changes in the thickness profiles of the three coats of the eye, and particularly that of the choroid, can be predicted from the degree of induced refractive error. METHODS: Hatchling chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were refracted using retinoscopy and were then sacrificed, and whole eyes were processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous sclera (CS) thickness measurements were made from photographic collages of the entire circumference of the globe. Of the 23 chickens, complete morphological profile data were available for both eyes of 10 animals (nine treated and one normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens were used as experimental controls as paired comparisons for statistical analyses. RESULTS: Morphological profiles of control and experimental eyes revealed significant systematic regional variations in tissue thickness. This variation was related to nasal or temporal eccentricity with the nasal side generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM and DIM eyes showed very similar anatomical responses despite significantly different degrees of refractive change. DIH eyes showed significant increases in choroidal thickness but none in retinal or CS thickness. Analysis of fellow control eyes indicated that in both myopia models (FDM and DIM), significant changes in all tissues of the untreated fellow eyes occur whereas only the choroid of the fellow eye was affected in the hyperopic (DIH) model. CONCLUSIONS: The morphological similarity observed in the circumferential profiles of the retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite approximately 20 D difference in final refraction suggests that choroidal thickness is not a good predictor of final refractive error across models. Similarly, the final refractive difference of approximately 20 D between the DIM and the DIH eyes did not receive a major contribution from the final difference in choroidal thickness (with its implied effect on vitreous chamber length).

Animals↗
PubMed2000

The role of photoreceptors in the control of refractive state.

The current state of research into experimentally induced refractive errors is reviewed. The area is analysed in three components-the transduction of defocus or deprivation, the vector for transmitting the error message from the retina to the outer tunics of the eye, and the identity of the effector for causing growth modulation in the sclera. Anatomical, pharmacological, electrophysiological and optical factors are considered in terms of which elements of the retina are necessary to support a refractive response to deprivation or defocus. Two of the current models are discussed-one emphasizing the role of the choroid in effecting ocular and refractive change, while the second model approaches the problem from the aspect of scleral changes that are associated with growth adaptation without emphasis on the error detection mechanism. A third model is proposed in which the error signal for deprivation or defocus is detected in the outer retina and where error is translated through separate signals for stimulus brightening and darkening into a net signal for fluid flow across and under the active control of the retinal pigment epithelium with the fluid communication between the vitreous chamber and the choroidal lymphatics. The directions of research both fundamental and clinical which are needed to create pharmaceutical or environmental solutions to refractive control are discussed.

Animals↗
PubMed1999

Cone receptor sensitivity is altered in form deprivation myopia in the chicken.

PURPOSE: The effect of form deprivation myopia (FDM) on cone photoreceptor function was investigated. METHODS: Photopic electroretinogram (ERG) a-waves were recorded from control and form-deprived eyes of chickens. Cone-generated P3 responses were derived from the leading edge of ERG a-waves using an analytical expression derived from a quantitative model of phototransduction. The parameters obtained were the maximum cone P3 response (RmaxP3), sensitivity (S), and delay (t(d)). RESULTS: P3 response sensitivity is significantly higher in form-deprived eyes, at lower retinal irradiances. At higher flash intensities, in form-deprived eyes, P3 response sensitivity declines at a significantly greater rate, per unit increase in retinal irradiance, than in control eyes. Visual deprivation does not significantly affect RmaxP3 or t(d). CONCLUSIONS: Hypotheses to explain the altered cone photoreceptor sensitivity in form-deprived eyes are proposed. Changes in the biochemistry of phototransduction, or intrinsic geometric and physical attributes of photoreceptors or their waveguide modal properties, could account for the findings.

Animals↗
PubMed1999

A role for choroidal lymphatics during recovery from form deprivation myopia?

BACKGROUND: The choroid of the chick swells markedly during recovery from experimentally induced myopia. It has been demonstrated previously that the lymphatic sinusoids of the choroid contribute most to the expansion. This raises important questions about the particular ultrastructural changes occurring in choroidal lymphatics as a means of understanding the role these vessels might play in emmetropization. METHODS: Thirteen hatchling chicks were monocularly occluded for 2 weeks to induce myopia and then allowed normal visual experiences during recovery for periods of 0 to 72 h before sacrifice. RESULTS: Electron microscopic analysis detailed the temporal progression of vascular changes and provides qualitative evidence for edema in the extravascular space. Quantitative analysis showed that the frequency of open junctions between lymphatic endothelial cells (an indicator of passive fluid transfer) increased over the 3 days of recovery. Lymphatic fenestrations (an indicator of active fluid transfer) were rare in both nondeprived eyes and in form-deprived eyes at the time of occluder removal, but increased in density significantly over the first 24 h of recovery before returning to control levels by 72 h. The number of lymphatic endothelial caveolae did not change significantly during recovery, nor did the number of fenestrations along the walls of choriocapillaris vessels. CONCLUSIONS: The walls of the lymphatics of the chick choroid open to allow greater fluid transfer during re-emmetropization than normal; the lymphatics may play an important role in the maintenance of chorioretinal fluid balance and homeostasis.

Animals↗
PubMed1998

Temporal analysis of the topographic ERG: chromatic versus achromatic stimulation.

The topographic electroretinogram evoked by multi-focal exchange of black and white or red and green stimuli was analysed into linear and non-linear Wiener kernels. The first-order (temporally linear) response showed a biphasic waveform which inverted as the luminance ratio of the exchanged colours passed through unity (established both psychophysically and photometrically). A short latency non-linearity which was dependant on luminance contrast was observed in both chromatic and achromatic ERG. However, in the chromatic second-order response, a long-latency non-linearity, foveally prominent, with a distinct skew in power towards the nasal retina, appeared around the isoluminant point, between the points of silent substitution for the L and M-cone types. Modelling of the second-order responses showed that over a wide range of luminance ratios, the chromatic ERG is well described by a linear combination of the achromatic (contrast-dependent) component and the response at isoluminance. The difference in second-order response between coloured and black and white stimulation, at the same luminance contrast, showed that the long-latency non-linearity is recorded when the red and green cone types are operating out of phase and peaks in amplitude at a green/red luminance ratio of 0.8. This interpretation was confirmed by the lack of the long-latency non-linearity in colour-anomalous subjects (whether deficient in the L or the M-cone type). A marked similarity exists between the properties of the long-latency non-linearity and the frequency-doubled response generated in the ganglion cells of the magnocellular pathway.

Color Perception↗
PubMed1998

Temporal analysis of the chromatic flash VEP--separate colour and luminance contrast components.

Temporal analysis of the chromatic flash visual evoked potential (VEP) was studied in human subjects with normal and anomalous colour vision using a deterministic pseudo-random binary stimulus (VERIS). Five experiments were carried out on four normal subjects investigating heterochromatic red-green exchange and single colour/achromatic (either red/grey or green/grey) exchange over a wide range of luminance ratios for the two stimuli, the effects of lowered mean luminance on the chromatic VEP and the effects of colour desaturation at constant mean luminance and constant luminance contrast. Finally, the performance of three dichromats, a protanope and two deuteranopes, on heterochromatic exchange VEP and on colour desaturation were investigated. In contrast to the chromatic electroretinogram, which shows great symmetry with respect to luminance ratio on opposite sides of the isoluminant point, the chromatic VEP demonstrated a distinct asymmetry when the colours exchanged included red. On the red side of isoluminance (red more luminant than green), a wave with longer latency and altered waveform became dominant. The effects of green stimulation were indistinguishable from those of achromatic stimulation at the same luminance contrast over the whole range of chromatic contrast and for all levels of desaturation studied. Desaturation of red with constant luminance contrast (desaturated red/grey stimulation) resulted in a systematic alteration in the evoked waveform. Subtraction of the achromatic first- and second-order responses from responses recorded in the red desaturation series resulted in remarkably uniform waveforms, with peak amplitudes growing linearly with saturation. The absence of interaction between achromatic and coloured components for all (including the most intense colour) stimulus parameters used suggests that the generators of these components are separate. Recordings from the dichromats showed that the contrast response minimum shifted from the point of photopic isoluminance to the point of zero cone contrast (at the silent substitution point) for the remaining cone type. The waveforms recorded with a series of luminance ratios were much simpler than those recorded from trichromats and symmetrical with respect to their isoluminant points. Despite the indication of the presence of L cones of apparently normal spectral sensitivity in the deuteranopes (on the basis of flicker photometry), there was no evidence for a red-sensitive component in the desaturation or heterochromatic stimulation series. The results are discussed in terms of the possibility of separate generation of chromatic and achromatic contributions to the VEP.

Color Perception↗
PubMed1998

Development of a magnocellular function in good and poor primary school-age readers.

BACKGROUND: Abnormal functioning of the transient visual pathway (the M-pathway) has been implicated in specific reading disability (SRD). The aim of this study is to examine the contrast thresholds for flicker-defined form discrimination in primary school children, and to compare its development with reading and mentation development as a means of identifying children at risk of SRD. METHODS: One hundred eighty-seven children (aged 4 to 13 years) and 22 adults (aged 18 to 45 years) were assessed for contrast sensitivity to an illusory, flicker contrast-defined form (the letter 'E')--a task which was designed to rely to a large extent on magnocellular pathway function. Reading age (Neale Analysis of Reading) and mental age (Raven's Coloured Progressive Matrices) were assessed in the children, who had been previously screened for clinically normal binocular vision and refractive anomalies. RESULTS: The ability of primary school-age children to discriminate the orientation of the low contrast flickered letters (from a choice of 4) showed a significant improvement from kindergarten (ages 4 to 6 years) to grade 3 (ages 8 to 10 years) and older age groups. No significant difference was found between good and disabled readers (at least 1-year lag in reading readiness for the kindergarten group and 2-year lag in reading performance for 8 to 10 and 10 to 12-year-olds). CONCLUSIONS: It appears that there is a developmental improvement in perceptual capacity for tasks attributed to magnocellular function, which plateaus at the age of about 8 to 10 years. However, despite the reported reduction of magnocellular function in specific reading disabled children, no significant difference in contrast threshold for flicker-defined letter discrimination was found between good and poor readers.

Adolescent↗
PubMed1998

Anomalies of genetic development as predictors of oculo-visual abnormalities in velo-cardio-facial syndrome.

BACKGROUND: Subjects with velo-cardio-facial syndrome (VCFS) were assessed to determine whether the learning disabilities (LDs) characterizing the syndrome are compounded by visual function deficits, which would be predicted on the basis of the proposed embryonic derivation of the genetic anomaly. METHODS: Twelve subjects diagnosed with VCFS underwent a vision screening with emphasis on binocular function. RESULTS: Subjects exhibited deficits in accommodation (N = 5), convergence (N = 7), fusional reserves (N = 9), and stereopsis (N = 10). Three patients were strabismic at near. No patient was in the clinically normal range for all tests of binocular function. CONCLUSIONS: Individuals with VCFS have a chromosome 22 deficit thought to alter the migration of neural crest (NC) cells, which are the embryonic precursors of the autonomic innervation of the smooth muscle components of the eye and of cranial nerves III, IV, and VI. It was predicted that VCFS patients would demonstrate reduced accommodation and convergence flexibility, which would reduce visual comfort for near work. The pathological etiology of the visual anomalies suggests that if visual training is not successful, these patients should be provided with a suitable optical reading correction from an early age.

Accommodation, Ocular↗
PubMed1998

Motion perception in global versus local attentional modes.

PURPOSE: Global and local attention are two forms of selective visual attention which activate different areas of the cortex. The purpose of this experiment was to test subjects' motion coherence thresholds under conditions of global or local attention. It was hypothesized that thresholds in global attention would be lower than in local attention. METHODS: Eleven adult subjects participated in this study. Subjects were required to identify direction of motion at variable coherence levels, while simultaneously identifying either the global or local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s). RESULTS: The results showed that letter identification (global or local) did not significantly affect motion coherence thresholds; however, thresholds were significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS: These results highlight the attentional limitations of visual information shown by increased motion coherence thresholds when two objects must be identified simultaneously in a brief display.

Adolescent↗
PubMed1998

Effects of peripheral flicker masking on M- and P-pathway response.

PURPOSE: The effects of metahue and metacontrast masking on the responses of the M- and P-pathways of the human visual system were investigated using temporal analysis of the multifocal flash visually evoked potential (VEP) (VERIS system). METHODS: The experiments were carried out at three achromatic luminance contrasts, 24, 70 and 96%, with three peripheral masks: a steady 65% grey mask, a grey flicker mask and an isoluminant red/green flicker mask. The stimuli were viewed monocularly and the mask and VERIS stimuli superposed with a mirror-aperture system. RESULTS/CONCLUSIONS: The masks had no significant effect on the behaviour of the M-pathway as stimulus contrast increased. The amplitude of the P-pathway was found to be approximately level at all contrasts of the stimulus and with all three masks rather than showing the expected steady increase in activity with increasing stimulus contrast.

Adult↗
PubMed1998

Anatomical correlates of experimentally induced myopia.

PURPOSE: The present study compares morphological changes associated with optical defocus-induced myopia (ODM) with those from form deprivation myopia (FDM), as it is yet to be determined whether the latter is a consequence of visual deprivation or active myopic eye growth. METHODS: Hatchling chicks were reared for 2 weeks wearing a monocular translucent occluder or -10.00 D lens, with the other eye used as a control. After enucleation, eyes were processed for scanning electron microscopy. RESULTS: Anatomical profiles of control eyes revealed significant variations in tissue thickness as a function of nasotemporal location. Both FDM and ODM eyes demonstrated similar morphological profiles of retinal thinning, cartilaginous scleral thickening, enlarged photoreceptor inner segments and decreased photoreceptor cell density towards the ora serrata. A graded differential orientation of photoreceptors existed in all eyes. CONCLUSION: The comparable morphological changes in FDM and ODM suggest that the response to altered visual experience is similar in both paradigms.

Animals↗
PubMed1998

Attentional blink in global versus local attentional modes.

PURPOSE: Brain imaging studies have shown that global and local attention activate different areas of the brain, with implication for dependence of perception on attentional state. The aim of the present experiment was to investigate the duration of the attentional blink in global versus local attention. METHODS: Rapid Serial Visual Presentation (RSVP) sequences of global/local stimuli were presented to 34 adult subjects who had to identify a target red figure followed by a determination of whether a certain probe letter, 'X' (specified to be either the global or local form), was present in the subsequent string of letters. RESULTS: Attentional blinks were longer than any previously reported (1.67 s global; 2.97 s local) and were significantly different.Thus, the length of the attentional blink is dependent on the attentional state of the subject. CONCLUSION: This pattern of results is consistent with the hypothesis that global attention mechanisms receive predominantly M-pathway input.

Adolescent↗
PubMed1997

Separate magnocellular and parvocellular contributions from temporal analysis of the multifocal VEP.

Temporal analysis of the multifocal cortical visual evoked potential (VEP) was studied using pseudo-random (m-sequence) achromatic stimulation. The effects of variation of luminance contrast on the first-order response were complex. At low to mid contrasts (< 60%), a wave doublet (P100-N115) predominated. A second wave complex (N100-P120-N160) dominated at high contrasts. The second-order responses, however, showed an extremely simple variation with luminance contrast. Intrinsic differences in the adaptation time of the generators of these two components caused a distinct separation in the slices of the second-order response. A rapidly adapting nonlinearity saturating at low contrasts was only observable when measuring the responses from two consecutive flashes. Its latency coincided with the contrast saturating first-order response component. By comparison, the nonlinearity derived from the responses to the stimuli with longer interstimulus intervals (second and third slices) yielded a much more linear contrast response function with lower contrast gain and latencies, which clearly corresponded to the longer latency component of the first-order response. Thus, the second-order responses show a first slice which is predominantly driven by neural elements that have a latency and contrast function that mimic those of the magnocellular neurons of the primate LGN and a second slice which is dominated by a generator whose properties resemble primate parvocellular function. This division into magno and parvocellular contribution to the VEP is based on function (interaction time) as distinct from other currently available analyses, with potential for neural analysis of visual disease.

Adult↗
PubMed1997

Lymphatic sinusoids exist in chick but not in rabbit choroid.

PURPOSE: Although it is generally thought that lymphatics do not exist in the choroid, there is mounting evidence that lymphatic-like structures do exist in primates and fowl. METHODS/RESULTS: Our comparison of the ultrastructure of chick and rabbit outer choroid indicates that major differences exist in the non-vascular areas of the choroid: notably, the chick has large lymphatic sinusoids, whereas the rabbit only has a system of large vacuoles contained within the processes of individual fibroblasts. CONCLUSIONS: These results raise questions regarding the similarities or otherwise between species of the management of retinal metabolites, excess tissue fluid and choroidal homeostasis, especially during conditions of overload.

Animals↗