Simultaneous Expression of UV and Violet SWS1 Opsins Expands the Visual Palette in a Group of Freshwater Snakes.

Snakes are known to express a rod visual opsin and two cone opsins, only (SWS1, LWS), a reduced palette resulting from their supposedly fossorial origins. Dipsadid snakes in the genus Helicops are highly visual predators that successfully invaded freshwater habitats from ancestral terrestrial-only habitats. Here, we report the first case of multiple SWS1 visual pigments in a vertebrate, simultaneously expressed in different photoreceptors and conferring both UV and violet sensitivity to Helicops snakes. Molecular analysis and in vitro expression confirmed the presence of two functional SWS1 opsins, likely the result of recent gene duplication. Evolutionary analyses indicate that each sws1 variant has undergone different evolutionary paths with strong purifying selection acting on the UV-sensitive copy and dN/dS ∼1 on the violet-sensitive copy. Site-directed mutagenesis points to the functional role of a single amino acid substitution, Phe86Val, in the large spectral shift between UV and violet opsins. In addition, higher densities of photoreceptors and SWS1 cones in the ventral retina suggest improved acuity in the upper visual field possibly correlated with visually guided behaviors. The expanded visual opsin repertoire and specialized retinal architecture are likely to improve photon uptake in underwater and terrestrial environments, and provide the neural substrate for a gain in chromatic discrimination, potentially conferring unique color vision in the UV-violet range. Our findings highlight the innovative solutions undertaken by a highly specialized lineage to tackle the challenges imposed by the invasion of novel photic environments and the extraordinary diversity of evolutionary trajectories taken by visual opsin-based perception in vertebrates.

Preliminary Findings on the Optimization of Visual Performance in Patients with Age-Related Macular Degeneration Using Biofeedback Training.

Biofeedback training has been used to improve fixation stability in subjects with central vision loss, but the psychophysiological mechanisms underlying the functional improvements resulted was not reported. The aim of this study was to investigate the effects of microperimetric biofeedback training on different visual functions and self-reported quality of vision in subjects with age-related macular degeneration. This case-control study included six subjects (72.0 ± 6.1 years of age) diagnosed with age-related macular degeneration (wet or dry) with low vision (best corrected visual acuity ranging from 0.5 to 0.1 in the study eye) and five healthy volunteers (64.2 ± 3.7 years of age). Ophthalmological and functional examinations were obtained from all subjects twice with an approximately 3-month interval. Subjects with central vision loss performed 12 sessions (10 min each) of biofeedback training between the two examinations. Functional evaluation included: microperimetry, spatial luminance contrast sensitivities, color vision thresholds, visual acuity, and reading speed. Visual performance during daily activities was also assessed using a standardized questionnaire. The ratio (2nd/1st examination) of the spatial luminance contrast sensitivity at lower spatial frequencies were much higher for the training subjects compared with the controls. In addition, self-reported quality of vision improved after the training. The significant improvement of the visual function such as spatial luminance contrast sensitivity may explain the better self-reported quality of vision. Possible structural and physiological mechanisms underlying this neuromodulation are discussed.

Photoreceptor-specific light adaptation of critical flicker frequency in trichromat and dichromat observers.

The silent substitution paradigm offers possibilities to investigate and compare the temporal properties of mechanisms driven by single photoreceptor types, including the critical flicker frequency (CFF), in which the state of adaptation can be kept as invariant. We have (1) measured CFFs using triple silent substitutions to isolate L-, M-, and S-cone as well as rod-driven pathways under identical mean luminances and chromaticities; (2) repeated the CFF measurements at different mean luminances in order to validate the Ferry-Porter law (stating that the relationship between CFF and the log retinal illuminance-log I-is linear); and (3) compared these CFF versus log I functions for L-, M-, S-cone-, and rod-isolating stimuli for five trichromats and four X-linked dichromats (two protanopes, two deuteranopes). We show that the effects of luminance on the CFFs with silent substitution are comparable to those measured previously with chromatic stimuli. We found that M-cone-driven CFFs are smaller in trichromats than in protanopes. Furthermore, the slopes of the M-cone-driven CFF versus log I functions are smaller in trichromats. Possibly, the lacking L-cones are replaced by M-cones in these two protanopes and the CFF depends on cone density. Furthermore, we found that in trichromats, the slopes of the CFF-log I functions are smaller for M-cone- than for L-cone-isolating stimuli. This contradicts the current interpretation of the CFF-log I functions for chromatic stimuli, which states that CFF is mediated by the most strongly modulated photoreceptor type. Thus, the larger slopes that were previously found with medium-wavelength chromatic stimuli compared with long-wavelength chromatic stimuli seem to be the result of an addition of signals from different photoreceptors and do not necessarily result from M-cones being inherently faster.

Electroretinographical determination of human color vision type.

It has been previously demonstrated that electroretinography (ERG) elicited by heterochromatically modulated stimuli can be used for objective determination of color vision type. Color vision of trichromatic, deuteranopic, and protanopic participants was psychophysically assessed by the Cambridge Color Test and confirmed genetically. ERG responses to red and green lights modulating in counterphase at 12 and 36 Hz were recorded, while the fraction of red modulation was varied. At 36 Hz (and second harmonics at 12 Hz), the responses were minimal at red fractions that differed significantly in protanopes. At 12 Hz (fundamental component), the responses of the trichromats differed significantly compared to those of the dichromats. An improved protocol shows that the three subject groups can be separated with no overlap.

Contrasting effects of transcranial direct current stimulation on central and peripheral visual fields.

Recent research suggested that transcranial direct current stimulation (tDCS) can affect visual processing and that it can be useful in visual rehabilitation. Nevertheless, there are still few investigations on the subject. tDCS selectivity and the extent of its outcomes on visual perception are still to be assessed. Here, we investigate whether central and peripheral visual fields are equally affected by tDCS. We also tried to reproduce a previous work that has evaluated tDCS effects on the central visual field only (Kraft et al. 207:283-290, 2010). Fifteen healthy subjects participated in this randomized repeated-measure design study and received 1.5-mA anodal, cathodal and sham stimulation in different sessions, while performing 10-2 and 60-4 protocols in an automated perimeter. Anodal tDCS significantly decreased thresholds, but was limited to the most eccentric regions of the visual field measured (60°). This suggests that tDCS might be used for rehabilitation of peripheral visual field losses. We did not replicate the excitatory tDCS effect in the central visual field as previously reported by another group. Instead, we observed a trend toward an inhibitory (yet not statistically significant) effect of anodal tDCS on the central field. This might be explained by methodological differences. These results highlight that although tDCS is a technique with a low focality in the spatial domain, its effects might be highly focal in a functional domain. When taken together with previous findings, this also suggests that tDCS may have a differential effect on different retinotopic areas in the brain.

Transcranial direct current stimulation can selectively affect different processing channels in human visual cortex.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical activity. Nonetheless, information regarding its functional specificity and the extent by which visual performance can be modulated is still lacking. Here, we used vision as model to address if it differentially affects different cell groups in the stimulated area. We applied tDCS to the occiput and performed a series of visual tests in a sham-controlled repeated-measures design. Achromatic contrast sensitivity was assessed psychophysically during tDCS, with tasks designed to target specific spatial frequency (SF) channels, inferred ON, OFF channels and inferred magnocellular and parvocellular pathways of the visual system. Sweep visual evoked potential (sVEP) for contrast sensitivity and Vernier acuity was recorded before and after tDCS. Anodal tDCS significantly increased thresholds for luminance decrements (OFF) only for the inferred magnocellular thresholds. Although tDCS had no significant effects on Vernier or contrast sVEP thresholds, it modulated suprathreshold amplitudes for both tasks. Cathodal tDCS increased sVEP amplitudes at a low SF, decreased it at a medium, and had no effect at a high SF. Cathodal tDCS increased sVEP phase lags for low and decreased it for high SF (maximum change corresponding to change in apparent latency >6 ms). Cathodal and anodal stimulation decreased amplitudes of sVEP Vernier responses. Exclusive tDCS effects on magnocellular thresholds agree with reports of pathway-specific tDCS effects. The dependence of tDCS effects on SF and contrast levels further suggests that tDCS differentially affects different cell groups in the visual cortex.

Comparative study of photoreceptor and retinal ganglion cell topography and spatial resolving power in Dipsadidae snakes.

The diurnal Dipsadidae snakes Philodryas olfersii and P. patagoniensis are closely related in their phylogeny but inhabit different ecological niches. P. olfersii is arboreal, whereas P. patagoniensis is preferentially terrestrial. The goal of the present study was to compare the density and topography of neurons, photoreceptors, and cells in the ganglion cell layer in the retinas of these two species using immunohistochemistry and Nissl staining procedures and estimate the spatial resolving power of their eyes based on the ganglion cell peak density. Four morphologically distinct types of cones were observed by scanning electron microscopy, 3 of which were labeled with anti-opsin antibodies: large single cones and double cones labeled by the antibody JH492 and small single cones labeled by the antibody JH455. The average densities of photoreceptors and neurons in the ganglion cell layer were similar in both species (∼10,000 and 7,000 cells·mm(-2), respectively). The estimated spatial resolving power was also similar, ranging from 2.4 to 2.7 cycles·degree(-1). However, the distribution of neurons had different specializations. In the arboreal P. olfersii, the isodensity maps had a horizontal visual streak, with a peak density in the central region and a lower density in the dorsal retina. This organization might be relevant for locomotion and hunting behavior in the arboreal layer. In the terrestrial P. patagoniensis, a concentric pattern of decreasing cell density emanated from an area centralis located in the naso-ventral retina. Lower densities were observed in the dorsal region. The ventrally high density improves the resolution in the superior visual field and may be an important adaptation for terrestrial snakes to perceive the approach of predators from above.

In vitro evidence for mycophenolic acid dose-related cytotoxicity in human retinal cells.

PURPOSE: Mycophenolic acid (MPA) is an immunosuppressive agent that controls noninfectious uveitis. Intravitreal MPA delivery may be a potential adjuvant therapy in patients who have to discontinue steroid or immunosuppressive systemic therapy because of side effects. The aims of this study are to evaluate the in vitro effects of MPA over human retinal pigment epithelium (ARPE-19) and human Muller cells (MIO M-1). METHODS: ARPE-19 cells and MIO M-1 cells were exposed to 25, 50, and 100 µg/mL of MPA (Roche Bioscience, Palo Alto, CA) for 24 hours. Toxicity was evaluated by trypan blue dye-exclusion cell viability assay, caspase-3/7 apoptosis-related assay, and JC-1 mitochondrial membrane potential assay. RESULTS: The MPA (25 µg/mL and 50 µg/mL) did not cause reduction in cell viability or significant change in caspase-3/7 activity in both cell lines tested. Mycophenolic acid (100 µg/mL) caused a significant decrease in cell viability (P < 0.01) and higher caspase-3/7 activity (P < 0.05) in both cell lines compared with untreated cells. The JC-1 mitochondrial membrane potential did not show statistically significant differences for both cell lines and all concentration tested when compared with untreated controls (P > 0.05). CONCLUSION: Intraocular delivery may be a potential alternative for the treatment of noninfectious uveitis, either by intravitreal injection or sustained-release drug-delivery systems, in doses of 50 µg/mL or lower.

Morphological Plasticity of the Retina of Viperidae Snakes Is Associated With Ontogenetic Changes in Ecology and Behavior.

Snakes of the Viperidae family have retinas adapted to low light conditions, with high packaging of rod-photoreceptors containing the rhodopsin photopigment (RH1), and three types of cone-photoreceptors, large single and double cones with long-wavelength sensitive opsins (LWS), and small single cones with short-wavelength sensitive opsins (SWS1). In this study, we compared the density and distribution of photoreceptors and ganglion cell layer (GCL) cells in whole-mounted retinas of two viperid snakes, the lancehead Bothrops jararaca and the rattlesnake Crotalus durissus, and we estimated the upper limits of spatial resolving power based on anatomical data. The ground-dwelling C. durissus inhabits savannah-like habitats and actively searches for places to hide before using the sit-and-wait hunting strategy to ambush rodents. B. jararaca inhabits forested areas and has ontogenetic changes in ecology and behavior. Adults are terrestrial and use similar hunting strategies to those used by rattlesnakes to prey on rodents. Juveniles are semi-arboreal and use the sit-and-wait strategy and caudal luring to attract ectothermic prey. Our analyses showed that neuronal densities were similar for the two species, but their patterns of distribution were different between and within species. In adults and juveniles of C. durissus, cones were distributed in poorly defined visual streaks and rods were concentrated in the dorsal retina, indicating higher sensitivity in the lower visual field. In adults of B. jararaca, both cones and rods were distributed in poorly defined visual streaks, while in juveniles, rods were concentrated in the dorsal retina and cones in the ventral retina, enhancing sensitivity in the lower visual field and visual acuity in the upper field. The GCL cells had peak densities in the temporal retina of C. durissus and adults of B. jararaca, indicating higher acuity in the frontal field. In juveniles of B. jararaca, the peak density of GCL cells in the ventral retina indicates better acuity in the upper field. The estimated visual acuity varied from 2.3 to 2.8 cycles per degree. Our results showed interspecific differences and suggest ontogenetic plasticity of the retinal architecture associated with changes in the niche occupied by viperid snakes, and highlight the importance of the retinal topography for visual ecology and behavior of snakes.

Vision in click beetles (Coleoptera: Elateridae): pigments and spectral correspondence between visual sensitivity and species bioluminescence emission.

Among lampyrids, intraspecific sexual communication is facilitated by spectral correspondence between visual sensitivity and bioluminescence emission from the single lantern in the tail. Could a similar strategy be utilized by the elaterids (click beetles), which have one ventral abdominal and two dorsal prothoracic lanterns? Spectral sensitivity [S(lambda)] and bioluminescence were investigated in four Brazilian click beetle species Fulgeochlizus bruchii, Pyrearinus termitilluminans, Pyrophorus punctatissimus and P. divergens, representing three genera. In addition, in situ microspectrophotometric absorption spectra were obtained for visual and screening pigments in P. punctatissimus and P. divergens species. In all species, the electroretinographic S(lambda) functions showed broad peaks in the green with a shoulder in the near-ultraviolet, suggesting the presence of short- and long-wavelength receptors in the compound eyes. The long-wavelength receptor in Pyrophorus species is mediated by a P540 rhodopsin in conjunction with a species-specific screening pigment. A correspondence was found between green to yellow bioluminescence emissions and its broad S(lambda) maximum in each of the four species. It is hypothesized that in elaterids, bioluminescence of the abdominal lantern is an optical signal for intraspecifc sexual communication, while the signals from the prothoracic lanterns serve to warn predators and may also provide illumination in flight.

Intraocular straylight and contrast sensitivity after contralateral wavefront-guided LASIK and wavefront-guided PRK for myopia.

PURPOSE: To compare intraocular straylight measurements and contrast sensitivity after wavefront-guided LASIK (WFG LASIK) in one eye and wavefront-guided photorefractive keratectomy (WFG PRK) in the fellow eye for myopia and myopic astigmatism correction. METHODS: A prospective, randomized study of 22 eyes of 11 patients who underwent simultaneous WFG LASIK and WFG PRK (contralateral eye). Both groups were treated with the NIDEK Advanced Vision Excimer Laser System, and a microkeratome was used for flap creation in the WFG LASIK group. High and low contrast visual acuity, wavefront analysis, contrast sensitivity, and retinal straylight measurements were performed preoperatively and at 3, 6, and 12 months postoperatively. A third-generation straylight meter, C-Quant (Oculus Optikgeräte GmbH), was used for measuring intraocular straylight. RESULTS: Twelve months postoperatively, mean uncorrected distance visual acuity was -0.06 +/- 0.07 logMAR in the WFG LASIK group and -0.10 +/- 0.10 logMAR in the WFG PRK group. Mean preoperative intraocular straylight was 0.94 +/- 0.12 logs for the WFG LASIK group and 0.96 +/- 0.11 logs for the WFG PRK group. After 12 months, the mean straylight value was 1.01 +/- 0.1 log s for the WFG LASIK group and 0.97 +/- 0.12 log s for the WFG PRK group. No difference was found between techniques after 12 months (P = .306). No significant difference in photopic and mesopic contrast sensitivity between groups was noted. CONCLUSIONS: Intraocular straylight showed no statistically significant increase 1 year after WFG LASIK and WFG PRK. Higher order aberrations increased significantly after surgery for both groups. Nevertheless, WFG LASIK and WFG PRK yielded excellent visual acuity and contrast sensitivity performance without significant differences between techniques.

Effects of age and optical blur on real depth stereoacuity.

Stereoscopic depth perception utilizes the disparity cues between the images that fall on the retinae of the two eyes. The purpose of this study was to determine what role aging and optical blur play in stereoscopic disparity sensitivity for real depth stimuli. Forty-six volunteers were tested ranging in age from 15 to 60 years. Crossed and uncrossed disparity thresholds were measured using white light under conditions of best optical correction. The uncrossed disparity thresholds were also measured with optical blur (from +1.0D to +5.0D added to the best correction). Stereothresholds were measured using the Frisby Stereo Test, which utilizes a four-alternative forced-choice staircase procedure. The threshold disparities measured for young adults were frequently lower than 10 arcsec, a value considerably lower than the clinical estimates commonly obtained using Random Dot Stereograms (20 arcsec) or Titmus Fly Test (40 arcsec) tests. Contrary to previous reports, disparity thresholds increased between the ages of 31 and 45 years. This finding should be taken into account in clinical evaluation of visual function of older patients. Optical blur degrades visual acuity and stereoacuity similarly under white-light conditions, indicating that both functions are affected proportionally by optical defocus.

Color vision impairment in type 2 diabetes assessed by the D-15d test and the Cambridge Colour Test.

Color vision impairment emerges at early stages of diabetes mellitus type 2 (DM2) and may precede diabetic retinopathy or the appearance of vascular alterations in the retina. The aim of the present study was to compare the evaluation of the color vision with two different tests - the Lanthony desaturated D-15d test (a traditional color arrangement test), and the Cambridge Colour Test (CCT) (a computerized color discrimination test) - in patients diagnosed with DM2 without clinical signs of diabetic retinopathy (DR), and in sex- and age-matched control groups. Both color tests revealed statistically significant differences between the controls and the worst eyes of the DM2 patients. In addition, the degree of color vision impairment diagnosed by both tests correlated with the disease duration. The D-15d outcomes indicated solely tritan losses. In comparison, CCT outcomes revealed diffuse losses in color discrimination: 13.3% for best eyes and 29% for worst eyes. In addition, elevation of tritan thresholds in the DM2 patients, as detected by the Trivector subtest of the CCT, was found to correlate with the level of glycated hemoglobin. Outcomes of both tests confirm that subclinical losses of color vision are present in DM2 patients at an early stage of the disease, prior to signs of retinopathy. Considering the advantages of the CCT test compared to the D-15d test, further studies should attempt to verify and/or improve the efficiency of the CCT test.

Color-space distortions following long-term occupational exposure to mercury vapor.

Color vision was examined in subjects with long-term occupational exposure to mercury (Hg) vapor. The color vision impairment was assessed by employing a quantitative measure of distortion of individual and group perceptual color spaces. Hg subjects (n = 18; 42.1 ± 6.5 years old; exposure time = 10.4 ± 5.0 years; time away from the exposure source = 6.8 ± 4.6 years) and controls (n = 18; 46.1 ± 8.4 years old) were examined using two arrangement tests, D-15 and D-15d, in the traditional way, and also in a triadic procedure. From each subject's 'odd-one-out' choices, matrices of inter-cap subjective dissimilarities were derived and processed by non-metric multidimensional scaling (MDS). D-15d results differed significantly between the Hg-group and the control group (p < 0.05), with the impairment predominantly along the tritan axis. 2D perceptual color spaces, individual and group, were reconstructed, with the dimensions interpreted as the red-green (RG) and the blue-yellow (BY) systems. When color configurations from the Hg-group were compared to those of the controls, they presented more fluctuations along both chromatic dimensions, indicating a statistically significant difference along the BY axis. In conclusion, the present findings confirm that color vision impairments persist in subjects that have received long-term occupational exposure to Hg-vapor although, at the time of testing, they were presenting mean urinary concentration within the normal range for non-exposed individuals. Considering the advantages of the triadic procedure in clinical evaluation of acquired color vision deficiencies, further studies should attempt to verify and/or improve its efficacy.

Structural Analysis of Glaucoma Brain and its Association With Ocular Parameters.

PRECIS: Glaucoma patients presented a decreased occipital pole surface area in both hemispheres. Moreover, these parameters are independently correlated with functional and structural ocular parameters. PURPOSE: The purpose of this study was to evaluate structural brain abnormalities in glaucoma patients using 3-Tesla magnetic resonance imaging and assess their correlation with associated structural and functional ocular findings. PATIENTS AND METHODS: This cross-sectional prospective study included 30 glaucoma patients and 18 healthy volunteers. All participants underwent standard automated perimetry, spectral-domain optical coherence tomography, and 3.0-Tesla magnetic resonance imaging. RESULTS: There was a significant difference between the surface area of the occipital pole in the left hemisphere of glaucoma patients (mean: 1253.9±149.3 mm) and that of control subjects (mean: 1341.9±129.8 mm), P=0.043. There was also a significant difference between the surface area of the occipital pole in the right hemisphere of glaucoma patients (mean: 1910.5±309.4 mm) and that of control subjects (mean: 2089.1±164.2 mm), P=0.029. There was no significant difference between the lingual, calcarine, superior frontal, and inferior frontal gyri of glaucoma patients and those of the control subjects (P>0.05 for all comparisons). The surface area of the occipital pole in the left hemisphere was significantly correlated with perimetry mean deviation values, visual acuity, age, and retinal nerve fiber layer thickness (P=0.001, <0.001, 0.010, and 0.006, respectively). The surface area of the occipital pole in the right hemisphere was significantly correlated with perimetry mean deviation values, visual field indices, visual acuity, age, and retinal nerve fiber layer thickness (P<0.001, 0.007, <0.001, 0.046, and <0.001, respectively). CONCLUSION: Glaucoma patients presented a decreased occipital pole surface area in both hemispheres that independently correlated with functional and structural ocular parameters.

Distribution and density of mixed-input ON bipolar cells of the goldfish (Carassius auratus) during growth.

Neurons are continuously produced at different rates and locations in the teleost retina. Goldfish rods are homogeneously distributed and maintain a stable density throughout growth, whereas little is known about their postsynaptic partners. We examined the distribution and density of mixed-input ON bipolar cells (ON mBCs) in 57 goldfish of various sizes by immunolabeling their retinas with an antibody against PKCα and counting PKCα-positive neurons in wholemounts. Cell densities were correlated with morphometric data for the same animals, and the spatial resolution of the ON mBC mosaic was calculated in each case. The distribution of ON mBCs is homogeneous throughout growth. For a 10-fold change in body size (i.e., from 20 to 200 mm), the total number of ON mBCs increases 2.8 times, while retinal area expands around 10 times. As a consequence, the density of ON mBCs in large fish falls to ∼1/3 of that of small animals, and intercellular spacing doubles. The eye and the lens become around three times larger from small to large fish. This causes the retinal magnification factor (and thereby the image projected onto retina) to augment by the same amount. Because the retinal magnification factor rises more than the intercellular spacing in the same animals, the spatial resolution of the ON mBC mosaic improves from 0.8 to 1.4 cycles/degree as the body size increases from 20 to 200 mm. As ON mBCs are mostly rod-driven, our results suggest that the scotopic acuity of the goldfish may improve as the animal grows.

Contributions of the Melanopsin-Expressing Ganglion Cells, Cones, and Rods to the Pupillary Light Response in Obstructive Sleep Apnea.

Purpose: To investigate the impact of obstructive sleep apnea (OSA) on the contribution of inner and outer retinal photoreceptors to the pupillary light response (PLR). Methods: Ninety-three eyes from 27 patients with OSA and 25 healthy controls were tested. OSA severity was graded according to the apnea-hypopnea index. PLR was measured monocularly with an eye tracker in a Ganzfeld in response to 1-second blue (470 nm) and red (640 nm) flashes at -3, -2, -1, 0, 1, 2, and 2.4 log cd/m2. Peak pupil constriction amplitude, peak latency, and the postillumination pupil response were measured. The Cambridge Colour Test, standard automatic perimetry, spectral domain optical coherence tomography, polysomnography, and the Pittsburgh Sleep Quality Index were used. Results: OSA patients have a significantly decreased peak pupil constriction amplitude for blue stimuli at -3, -2, -1, 1 log cd/m2 and at all red flash luminances (P < 0.050), revealing reduction of outer retina contributions to PLR. OSA patients showed reduced peak latency for blue (-2, 0, 2, 2.4 log cd/m2) and red stimuli (-2, 0 log cd/m2; P < 0.040). No significant difference was found in the melanopsin-mediated PLR. Conclusions: This study is the first to evaluate the inner and outer retinal contributions to PLR in OSA patients. The results showed that the outer retinal photoreceptor contributions to PLR were affected in moderate and severe OSA patients. In contrast, the inner retina contributions to PLR are preserved.

Thyroid hormone action is required for normal cone opsin expression during mouse retinal development.

PURPOSE: The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-beta gene, demonstrating an important role of thyroid hormone (TH) in retinal development. METHODS: The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand-binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding. RESULTS: Hypothyroid newborn mice showed an increase in S-opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TRbeta1 and -beta2 were T3-binding defective, the pattern of opsin expression was similar to TRbeta ablation, showing increased S-opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TRbeta were mutated in the helix 12 AF-2 domain. CONCLUSIONS: The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.

A computer-controlled color vision test for children based on the Cambridge Colour Test.

The present study aimed at providing conditions for the assessment of color discrimination in children using a modified version of the Cambridge Colour Test (CCT, Cambridge Research Systems Ltd., Rochester, UK). Since the task of indicating the gap of the Landolt C used in that test proved counterintuitive and/or difficult for young children to understand, we changed the target stimulus to a patch of color approximately the size of the Landolt C gap (about 7 degrees of visual angle at 50 cm from the monitor). The modifications were performed for the CCT Trivector test which measures color discrimination for the protan, deutan and tritan confusion lines. Experiment 1 sought to evaluate the correspondence between the CCT and the child-friendly adaptation with adult subjects (n = 29) with normal color vision. Results showed good agreement between the two test versions. Experiment 2 tested the child-friendly software with children 2 to 7 years old (n = 25) using operant training techniques for establishing and maintaining the subjects' performance. Color discrimination thresholds were progressively lower as age increased within the age range tested (2 to 30 years old), and the data--including those obtained for children--fell within the range of thresholds previously obtained for adults with the CCT. The protan and deutan thresholds were consistently lower than tritan thresholds, a pattern repeatedly observed in adults tested with the CCT. The results demonstrate that the test is fit for assessment of color discrimination in young children and may be a useful tool for the establishment of color vision thresholds during development.

Irreversible color vision losses in patients with chronic mercury vapor intoxication.

This longitudinal study addresses the reversibility of color vision losses in subjects who had been occupationally exposed to mercury vapor. Color discrimination was assessed in 20 Hg-exposed patients (mean age = 42.4 +/- 6.5 years; 6 females and 14 males) with exposure to Hg vapor during 10.5 +/- 5.3 years and away from the work place (relative to 2002) for 6.8 +/- 4.2 years. During the Hg exposure or up to one year after ceasing it, mean urinary Hg concentration was 47 +/- 35.4 mug/g creatinine. There was no information on Hg urinary concentration at the time of the first tests, in 2002 (Ventura et al., 2005), but at the time of the follow-up tests, in 2005, this value was 1.4 +/- 1.4 microg/g creatinine for patients compared with 0.5 +/- 0.5 microg/g creatinine for controls (different group from the one in Ventura et al. (2005)). Color vision was monocularly assessed using the Cambridge Colour Test (CCT). Hg-exposed patients had significantly worse color discrimination (p < 0.02) than controls, as evaluated by the size of MacAdam's color discrimination ellipses and color discrimination thresholds along protan, deutan, and tritan confusion axes. There were no significant differences between the results of the study in Ventura et al. (2005) and in the present follow-up measurements, in 2005, except for worsening of the tritan thresholds in the best eye in 2005. Both chromatic systems, blue-yellow and red-green, were affected in the first evaluation (Ventura et al., 2005) and remained impaired in the follow-up testing, in 2005. These findings indicate that following a long-term occupational exposure to Hg vapor, even several years away from the source of intoxication, color vision impairment remains irreversible.