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Biomedical subjects

L T Sharpe

Publications and source records attributed to L T Sharpe.

At least 55 records · Page 3Linked to original sources

Genetic heterogeneity among blue-cone monochromats.

Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.

Base Sequence↗

Wavelength discrimination as a function of field intensity, duration and size.

Wavelength discrimination was measured in 8 normal observers as a function of test field intensity (2.5-63 td), duration (0.5-5 sec) and dia (0.5-2 degrees) to determine the conditions under which the just noticeable difference (JND) is smallest. The wavelengths of the standard and comparison hemifields were always equated for the observer's sensation luminance. For field intensity and duration, the wavelength JND was found to decrease until these parameters were increased beyond a certain value--25 td and 1.0 sec, respectively--and to remain constant thereafter. For field diameter, however, the JND was smallest only within a very limited range of values--between 1.0 and 1.5 degrees--and increased sharply with smaller and larger values.

Adult↗

The field adaptation of the human rod visual system.

1. Incremental thresholds were measured in a retinal region 12 deg temporal from the fovea with a target of 200 ms in duration and 6 deg in diameter superimposed on background fields of various intensities and wavelengths. Measurements were made under rod-isolation conditions in five normal observers and in a typical, complete achromat observer who had no cone function. 2. The rise in threshold with background intensity changes with background wavelength in the normal trichromat observers. On 450, 520 and 560 nm backgrounds the average slope in logarithmic co-ordinates (0.78 +/- 0.04, S.D.) is similar to that found for the achromat--whose slope is independent of background wavelength (0.79 +/- 0.03)--but on a 640 nm background it more nearly approaches Weber's law (0.91 +/- 0.02). This indicates that the sensitivity of the rods to an incremental target is not determined by quantal absorptions in the rods alone but by quantal absorptions in both the rods and the cones. 3. Rod incremental thresholds were also measured in various colour-blind observers lacking one or more of the cone classes: a blue-cone monochromat, four deuteranopes and a protanope. For the blue-cone monochromat, like the achromat, the slope of the increment threshold curve is constant with background wavelength. For the deuteranopes and the protanope, like the normal, the slope increases with wavelength. The protanope, however, shows a smaller increase in slope, consistent with the lower sensitivity of his cones to long-wavelength light. 4. The dependence of the field adaptation of the rods on the cones was confirmed by field-mixture experiments, in which the incremental threshold was measured against bichromatic backgrounds, and in silent substitution experiments, in which backgrounds equated for their effects on either the cones or the rods but not both were instantaneously substituted for one another.

Adaptation, Ocular↗

Is colour vision possible with only rods and blue-sensitive cones?

At night all cats are grey, but with the approach of dawn they take on colour. By starlight, a single class of photoreceptors, the rods, function, whereas by daylight, three classes, the blue-, green- and red-sensitive cones, are active and provide colour vision. Only by comparing the rates of quantal absorption in more than one photoreceptor class is colour vision possible. Although the comparisons generally take place between the cones, they can involve the rods as well. Here we investigate the wavelength discrimination of an extremely rare group of individuals, blue-cone monochromats, who have only rods and one class of cones. We find that these individuals can distinguish wavelengths (440 to 500 nm) in the twilight region where the rods and blue-sensitive cones are simultaneously active.

Color Perception↗

Slow and fast pathways in the human rod visual system: electrophysiology and psychophysics.

Under most conditions, increasing the intensity of a flickering light makes the flicker more conspicuous. For a light flickering at 15 times per second, however, increasing the intensity can cause the flicker to disappear before reappearing again at higher intensities [Vision Res. 29, 1539 (1989)]. This flicker disappearance or null is also evident in human electrophysiological recordings at the same intensity levels. These results point to a duality within the rod visual pathway, in which flicker signals travel through a slow and a fast pathway and then recombine at a later stage. At 15 Hz the slow rod flicker signals are delayed by half a cycle relative to the fast signals. Thus, when the two signals are recombined, they destructively interfere and diminish the perception of flicker. The dual-pathway interpretation is supported by both electroretinographic and psychophysical evidence showing a phase difference of half a cycle between 15-Hz rod signals just below and just above the null region. These effects are apparent not only in the normal observer but also in an achromat observer who lacks functioning cone vision.

Electrophysiology↗

Contingent aftereffects: lateral interactions between color and motion.

A randomly dotted yellow disk was rotated at a speed of 5 rpm, alternating in direction every 10 sec. Its change in direction of rotation was paired with a change in surround color, which was either red or green. After 15 min of exposure, observers reported vivid motion aftereffects contingent on the color of both the stationary disk and the surround, even though during adaptation only motion or color was associated with either alone. In further experiments, it was established that a change in color (or direction of motion) of the disk could be associated with a change in direction of motion (or color) of the surround. Such lateral effects were found even when a wide (5 degree) annulus was introduced between the disk and the surround during adaptation and testing. Furthermore, the aftereffects generalized to the annulus, which was not associated with either color or motion during adaptation. However, when the disk alone was adapted to color and motion, no generalization to the surround was found (and vice versa), suggesting that the effects are not produced by adaptation of large receptive fields or by scatter of light within the eye. The results appear to conflict with the ideas that contingent aftereffects are confined to the adapted area of the retina and that they are built up by links between single-duty neurones, and with an extreme view of the segregation of color and motion early in human vision.

Adult↗

Estimating middle-wavelength and long-wavelength cone sensitivity with large, long-duration targets and small, brief targets.

Incremental threshold versus field-intensity curves (tvi) and spectral sensitivity functions were measured for 500 nm and 667 nm test flashes, either under the standard two-colour threshold conditions of Stiles (target: 1.0 deg, 200 ms)--which are known to favour detection by the chromatically-opponent pathways--or with a smaller (0.1 deg), shorter-duration (10 ms) target--chosen to favour detection by the non-opponent (achromatic) pathway. The data reveal differences between the two conditions: for the small, brief target, the tvi curves were shallower and less dependent upon wavelength, and the spectral sensitivity functions were narrower than for the standard target.

Color Perception↗

The incremental threshold of the rod visual system and Weber's law.

The incremental threshold of the isolated rod visual system is believed, under certain conditions, to obey Weber's law (that is, to increase in direct proportion to the intensity of the background). This relation was tested at several background wavelengths, over an intensity range for which the target was seen only by the rods. Although the slope on long-wavelength background approximates unity (that is, Weber's law on log-log coordinates), it averages less than 0.8 on short- and middle-wavelength backgrounds. This is the same value as that found for the thresholds of a typical, complete achromat--who lacks cone vision--regardless of background wavelength. These results force the conclusion that Weber's law for incremental threshold detection is achieved not by the rods alone but only by the rods acting together with the cones.

Dark Adaptation↗

Dark adaptation and increment threshold in rhesus monkey and man.

Dark adaptation and increment thresholds were determined for a trained rhesus monkey and a human observer under identical conditions. The measurements were made with a 1.5' diameter, 100 ms target at 10 degrees and 40 degrees eccentricity along the temporal horizontal meridian. Qualitatively, the results are similar for the two species: Both rhesus monkey and man have photopic and scotopic branches, which cross at approximately the same time in the dark and at approximately the same background luminance.

Adaptation, Physiological↗

Rod flicker perception: scotopic duality, phase lags and destructive interference.

Rod vision has a duality of organization: at mesopic luminances rod signals have access to a slow, sensitive pathway (which we refer to, following Stiles, as pi 0) and a fast, insensitive pathway (pi' 0). The phase lag between the two rod signals increases with frequency until at 15-Hz the rod signals transmitted through the two pathways emerge out-of-phase, so that destructive interference produces a nulling of the apparent flicker. Relative to the cones, the phase lag of pi' 0 is roughly half that of pi 0. Thus at 15-Hz pi' 0 signals can be out-of-phase with cone signals, so that the signals from the slower pathway, pi 0, are actually in phase with cone signals. We have investigated the frequency response, adaptation behavior and phase characteristics of the two rod processes. The slower process, pi 0 is more sensitive than pi' 0, and dominates from absolute threshold up to low mesopic levels. The adaptation of pi 0 seems not to be associated with a change in time constant, but rather with simple response compression or sensitivity scaling. The time constant of pi' 0, however, does change with adaptation. There are large differences in the way that light adaptation changes the sensitivity of the two processes: signals from pi'0 may evade part of the postreceptoral sensitivity regulating mechanism normally associated with rod vision. The ability of signals from pi 0 and pi' 0 to reinforce or cancel each other, however, suggests that they are later reunited in a common pathway.

Dark Adaptation↗

The photoreceptors in atypical achromatopsia.

1. The receptoral mechanisms underlying the vision of two atypical achromats of the complete variety were studied with standard psychophysical procedures. 2. Under scotopic conditions the spectral sensitivity of each achromat was well described by the CIE (Commission Internationale de l'Eclairage) scotopic sensitivity function and the recovery of sensitivity after a retinal bleach showed characteristic duplex behaviour with the time constant of recovery of the slower phase matching that of normal rod vision for both foveal and peripheral stimulation. 3. Their spectral sensitivity was measured under conditions of chromatic adaptation in order to reveal any residual middle or long wavelength cone activity. Only one photopic spectral responses was found and this was adequately described by the spectral sensitivity function of Stiles pi 3 mechanism of normal vision. 4. Increment threshold measurements as a function of background intensity revealed a double-branched function in the fovea. The lower branch was found to have the spectral sensitivity of the rods; the upper branch that of Stiles' pi 3 mechanism. Stiles-Crawford measurements of directional sensitivity confirmed that the branch with the rhodopsin action spectrum had the directional sensitivity of rods and that the branch with the action spectrum of pi 3 had the directional sensitivity of cones. 5. These was no evidence for hue discrimination under photopic conditions. Regions of apparently normal performance on hue discrimination tests on more careful examination could be explained by luminosity judgements mediated by short wavelength-absorbing receptors. 6. We reject the notion of there being rhodopsin-filled cones in the fovea of these subjects. The foveal and peripheral vision of each of these achromats can be adequately described in terms of the participation of only two types of receptor, namely normally functional rods under scotopic conditions and normally functioning short wavelength-absorbing cones under photopic conditions. They are therefore functional blue mono-cone monochromats, an explanation which was originally proposed by Blackwell & Blackwell (1957) over thirty years ago.

Color Vision Defects↗

Temporal summation in the achromat.

We investigated temporal summation of the rods in a complete achromat, who lacks cone vision. Critical duration (tc) was estimated both at the achromat's preferred area of fixation and at an area 12 deg laterally in the nasal visual field. Comparable tc determinations were made in a normal trichromat. At background luminances of 0.0 and 0.6 scot. td, where the rods mediate detection, the values of tc were similar for the achromat and the normal. At a luminance of 813 scot. tds, however, where the middle-wavelength sensitive cones mediate detection in the trichromat, the tc for the achromat was much longer than that for the trichromat.

Adaptation, Ocular↗

The directional sensitivity of the photoreceptors in the human achromat.

1. The anatomical nature of the retinal photoreceptors in a typical, complete achromat was investigated by measuring their directional sensitivity. 2. A small (0.5 deg), brief (94 ms) test flash was placed at threshold by varying either its intensity (indirect method) or the intensity of a large (5 deg) adapting field (direct method). The dependent variable was the intensity of light required for the detection threshold as a function of the position of entry in the pupil. An infra-red viewing system was used to monitor the achromat's pupil and eye position. 3. At both scotopic and mesopic adapting field luminances, the complete achromat's receptors displayed only a small directional sensitivity effect. The effect was not wavelength dependent and could be attributed solely to the rods. 4. The results are consistent with other psychophysical evidence indicating that the complete achromat's retinae lack the post-receptoral function of the cone photoreceptors. Therefore they do not confirm previous reports that complete achromats have a second, high-intensity type of photoreceptor.

Color Vision Defects↗

Proximity factor in color-difference evaluations.

The effect of dividing-strip width (sample proximity) upon sensitivity to suprathreshold and threshold color differences is explored by three methods that involve ratio comparisons, liminal determinations, and repeated color matchings. The results suggest, in general, that sample separation impairs lightness discrimination more than chromaticness discrimination and that it may be necessary to introduce a proximity factor into color-difference formulas when evaluating threshold or small-size color differences.

Adult↗