The color appearance of stimuli detected via short-wavelength-sensitive cones for breast cancer survivors using tamoxifen

This study compared color appearance data for two populations of middle-aged women: (1) women using the selective estrogen receptor modulator tamoxifen as adjuvant therapy following successful treatment for early-stage breast cancer, and (2) healthy amenorrheic (peri- or post-menopausal) control subjects not using any hormonally acting medications. A 3-alternative forced-response paradigm (with "blue", "lavender", or "white" as the allowable responses) was used for assessing the perceived color of 440-nm foveal test stimuli superimposed on a larger 3.6 log td 580-nm background. In contrast to the control subjects, the majority of tamoxifen users described the test stimuli as "white", whether at threshold or slightly suprathreshold. Threshold-sensitivity measurements themselves appeared less effective for distinguishing between subject groups. The results show that a simple color-naming procedure can reveal alterations of foveal short-wavelength-sensitive cone-mediated visual function that are common among tamoxifen users.     

Effect of a background on foveal and parafoveal cone dark adaptation

Psychophysical cone dark adaptation curves were measured in the fovea and the periphery. It appears that cone dark adaptation curves are identical in the fovea and the periphery when the measurements are made without any background illumination. A background illumination of 1.25 log td made the dark adaptation of the foveal cones slower than that of the cones at eccentricities of 1.5° and more.Apparently, the background affects the dynamic neuronal adaptation in a different way for the foveal cones than for the parafoveal cones.     

Temperature dependence of dark-adapted sensitivity and light-adaptation in photoreceptors with A1 visual pigments: A comparison of frog L-cones and rods

Flash responses of L-cones and rods were recorded as ERG mass potentials in the frog retina at different temperatures (2-25 °C). The purpose was to elucidate factors that make cones faster and less sensitive than rods, particularly the possible role of thermal activation of L-cone visual pigment in maintaining a “light-adapted” state even in darkness. Up to ca. 15 °C, cones and rods were desensitized roughly equally by warming (Q₁₀ ≈ 2.2-2.7), retaining a 5-fold sensitivity difference. In this range, the cone/rod difference must depend on factors other than thermal activation of the visual pigment. Above 15 °C, cones showed an additional component of desensitization compared with rods, coupled to accelerated response shut-off. This behavior is consistent with light-adaptation from temperature-dependent intrinsic activity (dark light). The apparent dark light as measured by the minimum background intensities needed to affect sensitivity and/or kinetics increased by ca. 10-fold between 15 and 25 °C, whereas reported increases in visual-pigment activation rates over this range are less than 5-fold. We conclude that the dark state of frog L-cones above 15 °C may be largely set by thermal activation of the phototransduction machinery, but only part of the experimentally determined dark light can be ascribed to the visual pigment.     

Spectral sensitivity of single cones in rainbow trout (Oncorhynchus mykiss): A whole-cell voltage clamp study

The UVS cone mechanism is known to light adapt at low intensities in comparison to other cones. We were interested in whether this property was related to higher sensitivity in UVS cones or to network adjustments in sensitivity. We investigated spectral sensitivity of 107 individual cone photoreceptors in rainbow trout (Oncorhynchus mykiss) using a whole-cell voltage clamp technique. Mean time-to-peak response was 339 ± 90 ms and flash sensitivity for a 100 ms flash was 4.37 × 10⁻³ ± 2.50 × 10⁻³ pA photons⁻¹ μm², with no significant differences between the UVS, SWS, MWS and LWS cone classes. The spectral sensitivity of the UVS, SWS and LWS cones conformed to the expression of SWS1, SWS2 and LWS opsin genes. The spectral sensitivity of MWS cones, however, showed clear evidence of co-expression of RH2a and RH2b opsin pigments. The fish used in this study bridged the ontogenetic stage where the MWS cones shift their expression from RH2b to RH2a.     

The structure of the cytoplasm of lens fibers as determined by conical tomography

Studies using conventional electron microscopy describe the cytoplasm of lens fiber cells as having essentially an amorphous structure. We hypothesized that significant structural detail might have been lost as a result of projecting the entire thickness of the section (50-100 nm) onto a single plane (the “projection artifact”). To test this hypothesis, we studied the 3D-structure of rat lens cortical fibers before and after extracting the “soluble” crystallins with low ionic strength buffers to make “ghosts.” Tomographic series in conical geometry were collected at 55° tilts and by 5° rotations until completing a 360° turn by low dose methods. They were aligned using fiduciary points, reconstructed with the weighted back projection algorithm and refined by projection matching. Analysis of the 3D-maps included semiautomatic density segmentation using a computer program based on the watershed algorithm. We found that the cytoplasm of cortical fibers, though appearing amorphous in regions of the highest density, was in fact comprised of an ordered structure resembling a “clustered matrix.” The matrix was comprised of thin (∼6 nm diameter) filaments bent sharply at 110-120° angles and studded with cube-shaped particles (the “beaded” filaments). In cortical fibers, the particles measured a = 14 ± 2, b = 13 ± 2 and c = 10 ± 2.4 nm (n = 30, mean ± SD) and were spaced at distances measuring 27.5 ± 2.4 nm apart (n = 8, mean ± SD), center-to-center. The matrix was formed as “beaded” filaments, bound to clusters of “soluble” proteins, crossed each other at nearly perpendicular angles. The matrix also made contact with the plasma membrane at a large number of distinct regions. We thus concluded that the cytoplasm of cortical lens fibers is comprised of a cytoskeletal matrix of “beaded” filaments that organize the “soluble” crystallins in separate regions. The association of this matrix with the plasma membrane allows the lens to maintain its structural integrity, while its association with crystallins yields its long-term transparency. Loss of either function likely would play a significant role in cataract formation.     

Anatomical and behavioral correlates of visual acuity in the Great Horned Owl

Light microscopy of the Great Horned Owl retina has revealed a well-defined convexiclivate fovea which contains both rods and cones. Comparative cell-density counts of rod and cone nuclei, cells of the inner nuclear layer, and ganglion cells for both foveal and peripheral nasal sections of retina indicate a marked decrease in convergence ratio and a small but significant increase in cones, foveally. Rods occur with a much higher density than cones in both retinal areas, but show no local increase in density across the center of the fovea.Behavioral, psychophysical studies of visual acuity over a wide range of luminances have indicated a maximum resolution in this species of 4–5 min of arc between 0–1.0 log ml. Although evidence was obtained for two different mechanisms mediating visual acuity at low vs. high luminance levels, both components of the acuity function 'appear to have a spectral sensitivity function similar to that of rhodopsin. Alternative hypotheses concerning the role of foveal rods vs. extrafoveal rods and foveal rods vs. foveal cones are suggested to account for the results obtained.     

Sensitivity of the blue-sensitive cones across the central retina

We measured increment thresholds up to 5° eccentricity using a 10′ dia flash viewed against 10⁴ td of 572-nm background. We found two distinct sensitivity profiles, one with flash wavelengths 410–470 nm and another with 520–580 nm. Spectral sensitivity plots indicate blue-sensitive cones and green-sensitive cones for the two profiles, respectively. Sensitivity of blue-sensitive cones is maximum at 1° eccentricity. Measurements at greater eccentricities are susceptible to adaptation to test field. The light-collecting area of blue-sensitive cones raised to a power follows the sensitivity profile of blue sensitive cones.     

Short-latency disparity vergence eye movements: a response to disparity energy

Vergence eye movements were elicited in human subjects by applying disparities to square-wave gratings lacking the fundamental (“missing fundamental”, mf). Using a dichoptic arrangement, subjects viewed gratings that were identical at the two eyes except for a phase difference of 1/4 wavelength so that, based on the nearest-neighbor matches, the features and the 4n + 1 harmonics (5th, 9th, etc.) all had binocular disparities of one sign, whereas the 4n − 1 harmonics (3rd, 7th, etc.) all had disparities of the opposite sign. Further, the amplitude of the ith harmonic was proportional to 1/i. Using the electromagnetic search coil technique to record the positions of both eyes indicated that the earliest vergence eye movements elicited by these disparity stimuli had ultra-short latencies (minimum, <65 ms) and were always in the direction of the most prominent harmonic, the 3rd, but their magnitudes fell short of those elicited when the same disparities were applied to pure sinusoids whose spatial frequency and contrast matched those of the 3rd harmonic. This shortfall was evident in both the horizontal vergence responses recorded with vertical grating stimuli and the vertical vergence responses recorded with horizontal grating stimuli. When the next most prominent harmonic, the 5th, was removed from the mf stimulus (creating the “mf-5” stimulus) the vertical vergence responses showed almost no shortfall—indicating that it had been almost entirely due to that 5th harmonic—but the horizontal vergence responses still showed a small shortfall, at least with higher contrast stimuli. This small shortfall might represent a very minor contribution from higher harmonics and/or distortion products and/or a feature-based mechanism. We conclude that the earliest disparity vergence responses—especially vertical—were strongly dependent on the major Fourier components of the binocular images, consistent with early spatial filtering of the monocular visual inputs prior to their binocular combination as in the disparity-energy model of complex cells in striate cortex [Ohzawa, I., DeAngelis, G. C., & Freeman, R. D. (1990). Stereoscopic depth discrimination in the visual cortex: neurons ideally suited as disparity detectors. Science, 249, 1037-1041].     

Central visual fields for short wavelength sensitive pathways in glaucoma and ocular hypertension

While conventional clinical visual acuity and kinetic visual fields may be essentially normal in ocular hypertension and early stages of glaucoma, other foveal aspects of vision (eg color, spatial and temporal contrast sensitivity) may be quite abnormal. Specifically, a selective vulnerability of the short wavelength sensitive (SWS) visual pathways in these conditions has previously been noted. Here we studied the central visual fields of 33 primary open angle glaucoma (POAG) patients, 32 ocular hypertensives (OHT), and 24 age-matched normal controls using blue and yellow test flashes on bright yellow backgrounds. SWS cone and MWS and/or LWS cone pathway sensitivities were measured at the fovea and at 2.5 degrees, 5 degrees, 10 degrees and 15 degrees eccentricities, in either the inferior temporal (for OHT) or horizontal nasal retina (for POAG). As expected, all groups had normal sensitivity to yellow flashes--detected by LWS and/or MWS cones--in these meridians. By comparison, for the blue flashes--detected by the SWS cones--the POAG and OHT groups had sensitivity deficits, uniformly across the central visual field, of about 6X and 1.8X, respectively, compared to normals. While six of 31 (19%) OHT subjects had localized glaucomatous field defects (greater than 0.4 log units) in the non-foveal inferior temporal retina, none of the 12 OHT subjects who were also tested in the horizontal nasal retina showed loss in this meridian. Finally, while no POAG subjects had localized sensitivity loss for yellow flashes in the horizontal nasal retina, four did show local field defects with blue test flashes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuronal adaptation to simulated and optically-induced astigmatic defocus

Purpose

It is well established that spatial adaptation can improve visual acuity over time in the presence of spherical defocus. It is less well known how far adaptation to astigmatic defocus can enhance visual acuity. We adapted subjects to “simulated” and optically-induced “real” astigmatic defocus, and studied how much they adapt and how selective adaptation was for the axis of astigmatism.

Methods

Ten subjects with a mean age of 26.7 ± 2.4 years (range 23-30) were enrolled in the study, three of them myopic (average spherical equivalent (SE) ± SD: −3.08 ± 1.42D) and seven emmetropic (average SE ± SD: −0.11 ± 0.18D). All had a corrected minimum visual acuity (VA) of log VA 0.0. For adaptation, subjects watched a movie at 4 m distance for 10 min that was convolved frame-by-frame with an astigmatic point spread function, equivalent to +3D defocus, or they watched an unfiltered movie but with spectacle frames with a 0/+3D astigmatic trial lenses. Subsequently, visual acuity was determined at the same distance, using high contrast letter acuity charts. Four experiments were performed. In experiment (1), simulated astigmatic defocus was presented both for adaptation and testing, in experiment (2) optically-induced astigmatic defocus was presented both for adaptation and testing of visual acuity. In all these cases, the +3D power meridian was at 0°. In experiments (3) and (4), the +3D power meridian was at 0° during adaptation but rotated to 90° during testing. Astigmatic defocus was simulated in experiment (3) but optically-induced in experiment (4).

Results

Experiments 1 and 2: adaptation to either simulated or real astigmatic defocus increased visual acuity in both test paradigms, simulated (change in VA 0.086 ± 0.069 log units; p < 0.01) and lens-induced astigmatic defocus (change in VA 0.068 ± 0.031 log units; p < 0.001). Experiments 3 and 4: when the axis was rotated, the improvement in visual acuity failed to reach significance, both for simulated (change in VA 0.042 ± 0.079 log units; p = 0.13) and lens-induced astigmatic defocus (change in VA 0.038 ± 0.086 log units; p = 0.19).

Conclusions

Adaptation to astigmatic defocus occurs for both simulated and real defocus, and the effects of adaptation seem to be selective for the axis of astigmatism. These observations suggest that adaptation involves a re-adjustment of the spatial filters selectively for astigmatic meridians, although the underlying mechanism must be more complicated than just changes in shapes of the receptive fields of retinal or cortical neurons.     

Contrast thresholds for letter identification in retinitis pigmentosa.

To assess mechanisms of foveal vision loss in retinitis pigmentosa (RP), contrast thresholds were measured for the identification of Sloan letters at four adapting field luminances (0.4, 1.4, 2.4, and 3.4 log td) in a group of 16 patients with RP who had best-corrected Snellen visual acuities of 20/30 or better, minimal or no posterior subcapsular cataracts, and no atrophic or cystic-appearing foveal lesions. Letter contrast sensitivities of the patients with RP were reduced below those of a group of ten subjects with normal vision for all letter sizes and at all adapting field luminances. The overall pattern of these results indicated that neither a reduced quantal absorption by foveal cones nor spatial undersampling from a loss of foveal cones accounted for the reductions in letter contrast sensitivities. The findings were most consistent with a uniform increase in intercone spacing in the foveas of this group of patients with RP and mild visual acuity loss.     

Visual sensitivity across the menstrual cycle

This study was designed to evaluate the hypothesis that hormonal change can affect lower level light-adaptation processes, which are likely to be retinally based. Foveal visual sensitivities were measured across several menstrual cycles of four women not using hormonally acting medication and across several menstrual cycles of three women using a triphasic oral contraceptive. One woman, diagnosed with premenstrual syndrome (PMS), was a subject for both groups. Sensitivities were measured for a series of test wavelengths for 580-nm backgrounds of 2.0 and 4.0 log td. Of the six individuals tested, one had clear evidence of visual-adaptation changes occurring in phase with the menstrual cycle. Prior to using the oral contraceptive, this individual (the PMS subject) experienced changes of short-wavelength-sensitive (SWS)-cone-mediated sensitivities of up to about 1.4 log unit on the 4.0 log td background. Her SWS-cone-mediated sensitivities tended to be highest near ovulation and lowest premenstrually. Threshold-versus-illuminance (TVI) curves confirmed that the rate of sensitivity decrease with increasing background illuminance (i.e. the TVI slope) was greater premenstrually. The degree of background-induced desensitization within her middle-wavelength-sensitive (MWS)/long-wavelength-sensitive (LWS) cone pathways also appeared to vary cyclically, but the magnitude of the variation was smaller and the time course appeared to be different. When this subject began oral contraceptive use, the patterns of sensitivity change were all altered. None of the other five subjects experienced changes of SWS-cone-mediated vision that were cyclic and significantly adaptation-state dependent. However, there was evidence for a limited degree of cyclic adaptation change within the MWS/LWS cone pathways of at least one additional subject. We conclude that hormonal change can--for some unknown proportion of women--be linked to alterations of retinal function. However, the alterations are not the same for all visual pathways, and there are pronounced individual differences. The data also demonstrate that individuals' visual adaptation capabilities can vary substantially over periods of weeks.     

Consensual pupillary light response in the red-eared slider turtle (Trachemys scripta elegans)

Purpose of this study was to determine if the turtle has a consensual pupillary light response (cPLR), and if so, to compare it to its direct pupillary light response (dPLR). One eye was illuminated with different intensities of light over a four log range while keeping the other eye in darkness. In the eye directly illuminated, pupil diameter was reduced by as much as ∼31%. In the eye not stimulated by light, pupil diameter was also reduced but less to ∼11%. When compared to the directly illuminated eye, this generated a ratio, cPLR-dPLR, equal to 0.35. Ratio of slopes for log/linear fits to plots of pupil changes versus retinal irradiance for non-illuminated (−1.27) to illuminated (−3.94) eyes closely matched at 0.32. cPLR had time constants ranging from 0.60 to 1.20 min; however, they were comparable and not statistically different from those of the dPLR, which ranged from 1.41 to 2.00 min. Application of mydriatic drugs to the directly illuminated eye also supported presence of a cPLR. Drugs reduced pupil constriction by ∼9% for the dPLR and slowed its time constant to 9.58 min while simultaneous enhancing constriction by ∼6% for the cPLR. Time constant for the cPLR at 1.75 min, however, was not changed. Results support that turtle possesses a cPLR although less strong than its dPLR.     

The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS

This study was conducted to investigate whether augmentation of macular pigment (MP) enhances visual performance (VP). 121 normal subjects were recruited. The active (A) group consumed 12 mg of lutein (L) and 1 mg of zeaxanthin (Z) daily. MP optical density (MPOD) was assessed by customized heterochromatic flicker photometry. VP was assessed as best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity (CS), glare disability, photostress, and subjective visual function. Subjects were assessed at baseline; 3; 6; 12 months (V1, V2, V3 and V4, respectively). Central MPOD increased significantly in the A group (p < 0.05) but not in the placebo group (p > 0.05). This statistically significant increase in MPOD in the A group was not, in general, associated with a corresponding improvement in VP (p > 0.05, for all variables), with the exception of a statistically significant time/treatment effect in “daily tasks comparative analysis” (p = 0.03). At V4, we report statistically significant differences in mesopic CS at 20.7 cpd, mesopic CS at 1.5 cpd under high glare conditions, and light/dark adaptation comparative analysis between the lower and the upper MP tertile groups (p < 0.05) Further study into the relationship between MP and VP is warranted, with particular attention directed towards individuals with low MP and suboptimal VP.     

Dark adaptation during transient hyperglycemia in type 2 diabetes

It was the purpose of the present study to examine dark adaptation in subjects with type 2 diabetes during transient hyperglycemia. Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to undergo an oral glucose tolerance test (OGTT) or to remain fasting. Dark adaptometry was measured in one eye, chosen at random, using a computer-controlled dark adaptometer. Dark adaptation and capillary blood glucose were measured at baseline and 80 minutes into the OGTT/fasting test. Blood glucose remained stable throughout the examination in the 12 fasting subjects, whereas glycemia increased in the 12 OGTT subjects, from 8.6 ± 2.1 at baseline to 21.1 ± 3.6 mM after 80 min. In the OGTT group, four out of seven subjects with delayed dark adaptation at baseline reached normal values during hyperglycemia. All examined aspects of rod adaptation were accelerated by hyperglycemia (time to rod-cone break −26%; time to rod intercept −16%, rod sensitivity recovery slope (log units/min) +35%), whereas no measurable change in cone adaptation was seen. The results are consistent with rod adaptation being limited by glycemia and with rod adaptation being delayed in subjects with diabetes compared with healthy subjects, the delay being reversible in response to hyperglycemia.     

Photopic adaptation in the red-green spectral range

Spectral sensitivity curves were measured for foveal test flashes at absolute threshold, and on varying intensities of a blue-white background which stimulates long and medium wave cones about equally. The average data for three subjects could be fitted with a standard deviation of 0.028 log units by assuming independent responses in “L” and “C” mechanisms with peak sensitivity near 555 and 605 nm. The C mechanism was adapted only about 86% as much (in log units) as the L mechanism. It is proposed that post-receptoral processes are responsible for this difference in adaptation; the significance of post-receptoral adaptation in photopic and scotopic vision is discussed.     

Protanomaly without darkened red is deuteranopia with rods

The Rayleigh match, a color match between a mixture of 545 + 670 nm lights and 589 nm light in modern instruments, is the definitive measurement for the diagnosis of inherited red-green color defects. All trichromats, whether normal or anomalous, have a limited range of 545 + 670 nm mixtures they perceive to match 589 nm: a typical color-normal match range is about 50-55% of 670 nm in the mixture (deutan mode), while deuteranomals have a range that includes mixtures with less 670 nm than normal and protanomals a range that includes mixtures with more 670 nm than normal. Further, the matching luminance of the 589 nm light for deuteranomals is the same as for normals but for protanomals is below normal. An example of an unexpected Rayleigh match, therefore, is a match range above normal (typical of protanomaly) and a normal luminance setting for 589 nm (typical of deuteranomaly), a match called protanomaly “when the red end of the spectrum is not darkened” [Pickford, R.W. (1950). Three pedigrees for color blindness. Nature, 165, 182.]. In this case, Rayleigh matching does not yield a clear diagnosis. Aside from Pickford, we are aware of only one other report of a similar observer [Pokorny, J., & Smith, V. C. (1981). A variant of red-green color defect. Vision Research, 21, 311-317]; this study predated modern genetic techniques that can reveal the cone photopigment(s) in the red-green range. We recently had the opportunity to conduct genetic and psychophysical tests on such an observer. Genetic results predict he is a deuteranope. His Rayleigh match is consistent with L cones and a contribution from rods. Further, with a rod-suppressing background, his Rayleigh match is characteristic of a single L-cone photopigment (deuteranopia).     

Long-wave sensitivity in the masked greenling (Hexagrammos octogrammus), a shallow-water marine fish

Microspectrophotometry (MSP) revealed that surprisingly for a “fully marine” species, in summer, photoreceptors of the nearshore scorpaeniform fish known as the masked greenling, Hexagrammos octogrammus, contained exclusively, or presumably, porphyropsin with a small admixture of rhodopsin. As a result of this, the λ_max of the spectral sensitivity of the photoreceptors were significantly shifted to longer wavelengths as compared to the λ_max typical of marine shallow-water fishes, showing about 530 nm for rods and single cones, and 570/625 nm for double-cone members. These unique spectral shifts would permit a cone-driven wavelength discrimination in spite of high-density orange corneal filters which block light at lower wavelengths.     

Lateral interactions in the control of visual sensitivity

Threshold vs intensity curves for cone vision, measured in the parafoveal retina, quickly saturate if the adapting background is made small (e.g. 19′ at 5° eccentricity). Log increment threshold increases at a rate of about 3:1 with log background illuminance at levels as low as 10 td. This shows that lateral interactions are an important process in preserving differential sensitivity in cone vision across the wide range of illuminances over which it normally operates.Parallels between light and dark adaptation in the effect of field size were explored, since effects of comparable magnitude are observed in both. Backgrounds and bleaches equated for their effects at one field size do not have equal effects on threshold at other field sizes, however, with small-area bleaches raising threshold more than predicted. This failure of equivalence was also revealed in a second experiment, in which recovery of sensitivity following small area bleaches was measured in the presence of large steady background fields, which have the effect of lowering threshold. Thresholds following the small bleach were lowered less than expected on the basis of the “equivalent background” hypothesis, a result which we take to mean that signals from bleached cones exceed those produced by a background which has an equivalent effect on threshold (the “equivalent background”).Control experiments examined whether rods contribute to the overloading of cone response by small fields and the possible contribution of such central adaptation processes as spatial frequency adaptation.     

Discriminating “top-heavy” versus “bottom-heavy” geometric patterns in 2- to 4.5-month-old infants

Simion, Valenza, Macchi Cassia, Turati, and Umiltà (2002) suggested that newborns preferred “top-heavy” stimuli and such bias may account for neonatal face preference. However, convergent evidence for the discriminability between the top-heavy versus bottom-heavy patterns has not been demonstrated. We used a modified familiarization/novelty procedure (Chien, Palmer, & Teller, 2003) to assess basic discriminability between “top-heavy” and “bottom-heavy” geometric patterns in 2- to 4.5-month-old infants. Each infant was tested with three types of top-heavy and bottom-heavy geometric figures and received both familiarized-to-top-heavy and familiarized-to-bottom-heavy conditions. If infants of this age can discriminate the two configurations and there is no intrinsic bias toward either pattern, we expected to see significant and about equal novelty effects in both familiarization conditions. If there is a strong intrinsic bias for the top-heavy configuration, we expect to see a greater preference for the top-heavy patterns in the familiarization-to-bottom-heavy condition. Our results (N = 24) showed significant and equal novelty preferences in both familiarization conditions across age and figure types, suggesting a reliable discriminability between top-heavy and bottom-heavy configurations and there is no intrinsic bias towards either configuration at this age.