Brincat and Westheimer [Journal of Neurophysiology 83 (2000) 1900] have reported facilitating interactions in the discrimination of spatially separated target orientations and co-linear inducing orientations by human observers. With smaller gaps between stimuli (short-range effects), facilitating interactions were found to depend on the contrast polarity of the stimuli. With larger gaps (long-range effects), only co-linearity of the stimuli seemed necessary to produce facilitation. In our study, the dependency of facilitating interactions on the intensity (luminance) of line stimuli is investigated by measuring detection thresholds for a target line separated from the end of an inducing line by co-axial gaps ranging from 5 to 200 min of visual arc. We find facilitating interactions between target and inducing orientations, producing short-range and long-range effects similar to those reported by Brincat and Westheimer. In addition, detection thresholds as a function of the co-axial separation between target and inducing line reveal an interaction between the spatial regime of facilitating effects and the luminance of the stimuli. Short-range effects are found to be sensitive to changes in local intensity while long-range effects remain unaffected.
To evaluate the impact of intraocular (IOP) reduction on retinal ganglion cell (RGC) function measured using pattern electroretinogram optimized for glaucoma (PERGLA) in glaucoma suspect and glaucomatous eyes receiving latanoprost 0.005% versus placebo.
This was a prospective, placebo-controlled, double masked, cross-over clinical trial. One randomly selected eye of each subject meeting eligibility criteria was enrolled. At each visit, subjects underwent five diurnal measurements between 8:00 am and 4:00 pm consisting of Goldmann IOP, and PERGLA measurements. A baseline examination was performed following a 4-week washout period, and repeat examination after randomly receiving latanoprost or placebo for 4-weeks. Subjects were then crossed over to receive the alternative therapy for 4 weeks following a second washout period, and underwent repeat examination. Linear mixed-effect models were used for the analysis.
Sixty-eight eyes (35 glaucoma, 33 glaucoma suspect) of 68 patients (mean age 67.4 ± 10.6 years) were enrolled. The mean IOP (mmHg) after latanoprost 0.005% therapy (14.9 ± 3.8) was significantly lower than baseline (18.8 ± 4.7, p<0.001) or placebo (18.0 ± 4.3), with a mean reduction of -20 ± 13%. Mean PERGLA amplitude (μV) and phase (π-radian) using latanoprost (0.49 ± 0.22 and 1.71 ± 0.22, respectively) were similar (p > 0.05) to baseline (0.49 ± 0.24 and 1.69 ± 0.19) and placebo (0.50 ± 0.24 and 1.72 ± 0.23). No significant (p > 0.05) diurnal variation in PERGLA amplitude was observed at baseline, or using latanoprost or placebo. Treatment with latanoprost, time of day, and IOP were not significantly (p > 0.05) associated with PERGLA amplitude or phase.
Twenty percent IOP reduction using latanoprost monotherapy is not associated with improvement in RGC function measured with PERGLA.
We report a perceptual phenomenon that originates from a nonlinear operation during the visual process, and we use these observations to study the functional organization of the responsible nonlinearity; the regulation of visual sensitivity to light. When the contrast of a high frequency grating was modulated while its spatial and temporal average luminance was kept constant, observers saw brightness changes or desaturation in the field. If the contrast was modulated periodically between zero and a peak value, observers saw vivid flicker (contrast-modulation flicker), and this flicker could be seen even when the grating was too fine to be visually resolved as a pattern. This uniform-field flicker can be nulled by a modulation of space-average luminance at the contrast-modulation frequency, with appropriate phase and modulation depth. Contrast-modulation flicker is still measurable with gratings at 100 cycles/deg. The dynamics of contrast-modulation flicker suggest that it results from an early sensitivity-controlling mechanism, acting very rapidly (within about 20 msec). Its dependence on stimulus spatial frequency implies a strictly local luminance nonlinearity, one that either resides within individual photoreceptors or operates on signals from individual receptors.
Humans and monkeys mislocalize targets flashed around the time of a saccade. Here, we present data from three monkeys on a double-step task with a 100ms target duration. All three subjects mislocalized targets that were flashed around the time of the first saccade, in spite of long intersaccadic intervals. The error was consistently in the direction opposite that of the saccade, and occurred in some cases when the target presentation was entirely presaccadic. This is inconsistent with a theory invoking a damped representation of eye position, but it is consistent with the hypothesis that it is due to an error in peri-saccadic remapping.
The precision of smooth pursuit eye movements was described by means of a new dependent measure, the "oculomotor difference threshold" (analogous to the perceptual difference threshold) which represents the smallest difference in target velocity that produces statistically distinguishable differences in eye velocity. Oculomotor difference thresholds for constant velocity motions were largest (greater than 50% of target velocity) during the initial 200 msec of target motion, despite fairly high average gains (0.7-1.4) during the same period. Oculomotor difference thresholds declined over time. By about 600-700 msec after the onset of target motion they reached values as low as the perceptual difference thresholds measured psychophysically with the same target velocities. The similarity of the difference thresholds suggests that equally precise sensory representations of target velocity influenced perception and smooth eye movements. Nonsensory influences on smooth eye movement were also found. Smooth pursuit velocity: (1) depended on the velocity of targets in preceding trials; (2) was decreased during the initial 200 msec of target motion when the duration of motion was reduced from 1 sec to 200 msec, a result which shows that high initial pursuit velocity depends on the expectation that pursuit will continue. These effects of context and expected duration allowed the eye to achieve quickly a velocity close to that of the target it was most likely to encounter. Study of the precision of pursuit may be valuable for characterizing its sensory input, but study of the effects of the context in which a stimulus appears and the effects of expectations about future target motion may be more valuable for understanding how smooth eye movements guarantee retinal image velocities optimal for vision.
A biologically motivated computational model of bottom-up visual selective attention was used to examine the degree to which stimulus salience guides the allocation of attention. Human eye movements were recorded while participants viewed a series of digitized images of complex natural and artificial scenes. Stimulus dependence of attention, as measured by the correlation between computed stimulus salience and fixation locations, was found to be significantly greater than that expected by chance alone and furthermore was greatest for eye movements that immediately follow stimulus onset. The ability to guide attention of three modeled stimulus features (color, intensity and orientation) was examined and found to vary with image type. Additionally, the effect of the drop in visual sensitivity as a function of eccentricity on stimulus salience was examined, modeled, and shown to be an important determiner of attentional allocation. Overall, the results indicate that stimulus-driven, bottom-up mechanisms contribute significantly to attentional guidance under natural viewing conditions.
Age-related macular degeneration (AMD) is a complex disorder with genetic and environmental influences. The genetic influences affecting AMD are not well understood and few genes have been consistently implicated and replicated for this disease. A polymorphism (rs11200638) in a transcription factor binding site of the HTRA1 gene has been described, in previous reports, as being most significantly associated with AMD. In this paper, we investigate haplotype association and individual polymorphic association by genotyping additional variants in the AMD risk-associated region of chromosome 10q26. We demonstrate that rs11200638 in the promoter region and rs2293870 in exon 1 of HTRA1, are among the most significantly associated variants for advanced forms of AMD.
All-trans and 11-cis 3-hydroxyretinals were synthesized and the presence of these substances in the head of Drosophila melanogaster was shown by using high performance liquid chromatography. Even when the head extract was prepared in the dark from the flies reared successively in the dark, both of the 3-hydroxyretinal isomers were detected. In the culture medium, they were not present. D. melanogaster must have an 11-cis 3-hydroxyretinal forming-system that does not need light.
Small bleaches were used to study the rhodopsin regeneration process. At bleaches from 5.2% to 24.7%, the rhodopsin regenerations were consistent with a one-for-one recovery of bleached molecules. At response saturation rod photoreceptors exhibit a bleach level of only 5%. Major increases in rhodopsin regeneration were observed at bleach levels between 1.3% and 5.2%. The rhodopsin regenerations exhibited a linear relationship that was 4-times the bleach (dark adaptations of 0.75 and 1.5 h). The data show that the bleach initiates the availability, and possibly production, of 11-cis retinal in amounts that are 4-times the number of bleached molecules within the functional range of the rod photoreceptors. Rhodopsin regeneration also requires the presence of opsins without chromophore. Regenerations beyond the bleach indicate the presence of such opsins prior to the bleach. The opsin amounts were 8.1%, 8.6%, 3.1% and 0% of the total visual pigment at dark adaptation times of 0.75, 1.5, 24 and 48 h, respectively. Those opsins, as well as the ones produced by the bleach, may be regenerated to rhodopsin following a small bleach or with additional time in the dark.
The newly synthesized 11-cis-7-methylretinal can form an artificial visual pigment with kinetic and spectroscopic properties similar to the native pigment in the dark-state. However, its photobleaching behavior is altered, showing a Meta I-like photoproduct. This behavior reflects a steric constraint imposed by the 7-methyl group that affects the conformational change in the binding pocket as a result of retinal photoisomerization. Transducin activation is reduced, when compared to the native pigment with 11-cis-retinal. Molecular dynamics simulations suggest coupling of the C7 methyl group and the beta-ionone ring with Met207 in transmembrane helix 5 in agreement with recent experimental results.
The antischistosomal drug 1,5-di-(p-aminophenoxy) pentane (DAPP), an inhibitor of rhodopsin regeneration in the vertebrate retina, is shown to completely block the production of 11-cis-retinyl palmitate in the frog eye. An untreated frog generates a large amount of 11-cis-retinyl palmitate during 1-2 days in the dark after a strong bleach. Also, it is demonstrated that DAPP can deplete the stores of 11-cis-retinyl palmitate in the dark-adapted frog eye. The specificity of DAPP's inhibition of dark-adaptation is explored, and the usefulness of employing retinotoxic drugs to investigate the physiology and biochemistry of rhodopsin regeneration is discussed.
This work was designed to provide an insight into the mammalian visual cycle by investigating the possible function of retinoid-binding proteins in this system, and the distribution and type of 11-cis retinoids present in the interphotoreceptor matrix and the cytosols of the retinal pigment epithelium and retina. The total retinol and retinal in the soluble fractions from these three compartments was 8% (3.31 nmol/eye) of the retinyl palmitate and stearate stored in the pigment epithelium membrane fractions (39 nmol/eye). Only small amounts of retinoids were detected in the rod outer segment cytosol. The insoluble fractions also contained retinol, nearly all of which was found in the retina. The retinoids in the soluble fractions appeared to be bound to cellular retinol-binding protein (CRBP), cellular retinal-binding protein (CRA1BP) and interstitial retinol-binding protein (IRBP, a high-Mr glycoprotein). Using immunospecific precipitation, immunoblot and immunocytochemical techniques it was demonstrated that IRBP was localized in the interphotoreceptor matrix and was synthesized and secreted by the retina, a process that did not require the protein to be glycosylated. The amount of retinol bound to IRBP increased if the eyes were exposed to light, when it was estimated that the protein carried up to 30% of its full capacity for all-trans retinol. In addition to all-trans retinol, IRBP carried smaller amounts of 11-cis retinol. The proportion of 11-cis retinol was frequently higher in eyes that had been protected from illumination, suggesting that IRBP plays a role in rhodopsin regeneration during dark-adaptation. Additionally, endogenous 11-cis retinoids in the retina and RPE cytosols were bound to an Mr 33,000 protein tentatively identified as CRA1BP. The 11-cis retinoid in the retina cytosol was mainly in the form of retinol, while in the RPE cytosol it was mainly in the form of retinal. Substantial amounts of 11-cis retinol were also found in the insoluble (membrane) fraction from the retina. It is suggested that in the mammalian retina 11-cis retinol is generated from all-trans retinol (possibly in the Muller cells). Lack of an 11-cis retinol oxidoreductase in the retina prevents it from being utilized for rhodopsin regeneration until it has been transported to the pigment epithelium, where it is converted to 11-cis retinal and returned to the rod outer segments. It is also suggested that IRBP may be implicated in the transport of retinoids between the rod outer segments, the Muller cells and the pigment epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)
Cyclic GMP accumulates in visual cells of rd (retinal degeneration) mice before the onset of morphological pathology. Observations are presented which support the hypothesis that elevated levels of cyclic GMP initiate visual cell degeneration in some early-onset disorders causing blindness. The accumulation of cyclic GMP in rd visual cells results apparently from defective mechanisms that regulate cyclic GMP metabolism.
Using the head motion procedure, the apparent distance of a point of light in an otherwise dark visual field was measured under conditions in which oculomotor cues (accommodation, convergence) and absolute motion parallax were varied together and separately. It was concluded that absolute motion parallax is almost as effective a cue to distance as are oculomotor cues from monocular observation, but is not as effective as oculomotor cues from binocular observation. Evidence was also presented that the null adjustment method, used in conjunction with the head motion procedure, provides an unbiased measure of apparent distance.
Experiments were carried out to study the visibility of postsaccadic stimuli under the influence of patterns presented at the saccade goal immediately before the saccade. For gratings of 3.2 c/deg an improved visibility was found in the case when the pre- and postsaccadic stimuli have the same spatial frequency. This enhancement effect is also obtained with aperiodic patterns, and turns out to be pattern specific. Dichoptic experiments show that this effect is a central phenomenon. The experimental data can be interpreted as an integration of information about extra-foveal regions of the visual field at the saccade goal with later information obtained by foveal fixation after the eye movement. The results are discussed under the view point of visual stability.
To understand better the range of conditions supporting stereoscopic vision, we explored the effects of speed, as well as specific optic flow patterns, on judgments of the depth, near or far of fixation, of large targets briefly presented in the upper periphery. They had large disparities (1-6 deg) and moved at high speeds (20-100 deg/sec). Motion was either vertical or horizontal, as well as either unidirectional or layered in bands of alternating directions (opponent-motion). High stimulus speeds can extend dmax. The effects are explained by models having linear filters that signal both faster speeds and larger disparities. Stereo depth localization can also be enhanced by opponent-motion even when kinetic depth itself is not apparent. Improvements are greatest with wide-field, horizontal opponent-motion. The results imply functions such as vection, posture-control, and vergence may benefit from disparity information enhanced by optic flow patterns that are commonly available to a moving, binocular observer.
After an observer views an adapting pattern moving uniformly in one direction for a prolonged period of time, a stationary pattern will-appear to move in the opposite direction. In the present experiments observers inspected spatially periodic, adapting patterns which were moved at different speeds in different experimental conditions. The magnitude of the motion aftereffect which was generated in each condition was measured. There was an interaction between pattern characteristics and adapting speed. For a variety of patterns the temporal frequency, rather than the velocity, of the adapting patterns was the critical determinant of aftereffect magnitude. The psychophysical results suggest (1) that the responses of direction-sensitive analyzers in humans are controlled by the temporal frequency of drifting patterns rather than their velocity, and (2) that the peak response frequency of direction-sensitive analyzers is about 5 Hz under low photopic levels of illumination.
The response amplitude of simple cortical cells to spatiotemporal sine-wave patterns has been thoroughly documented in both cat and monkey. However, comparable measurements of response phase are not available even though phase measurements are essential for estimating the complete transfer function of a cell, and thus its spatiotemporal receptive field. This report describes a simple procedure for measuring both the amplitude and the phase transfer functions of striate cells. This technique was applied to 15 monkey and 27 cat simple cells. The spatiotemporal phase response functions were found to be adequately described by linear equations in four parameters. Both the amplitude and phase responses were found to satisfy several strong constraints implied by the class of linear quadrature models proposed recently in theories of biological motion sensitivity. Because the data satisfied these constraints, it was possible to determine four important receptive field properties from the phase data: the spatial symmetry, the temporal symmetry, the response latency, and the spatial position. The receptive fields were found to have a wide range of spatial symmetries, but a more narrow range of temporal symmetries. Spatiotemporal receptive fields reconstructed from complete transfer functions are used to illustrate some of the differences between direction selective and nondirection selective cells. Finally, the effects of linear and nonlinear mechanisms on amplitude, phase, and direction selective responses are considered.
The direct compensation method allows for an accurate (standard deviation below 0.05 log unit) determination of intraocular light scattering between 3.5 and 25 deg of scattering angle and is suitable for untrained subjects. The method was used to study population behaviour and individual variation in 129 volunteers between 20 and 82 yr of age, visual acuity equal to or better than one and no apparent eye pathology. The results indicate straylight to increase with the 4th power of age, doubling at 70. In addition to the age dependence, there was great variation between individuals. Part of this is due to negative correlation with pigmentation.