Short-wavelength Cone Research Articles

The Effect of Spectral Power Distribution on the Perception of Scene Brightness in Nighttime Lit Streets

A laboratory experiment and two field experiments were conducted to investigate the effects of lamp spectral power distribution on perceived scene brightness in nighttime lit streets and reveal the mechanisms of the perception of scene brightness. The experimental results confirmed the Purkinje effect in which a scene appears brighter when it is illuminated by lamps with enriched short-wavelength radiation. The results also suggest that perceived scene brightness corresponds to mesopic luminances within the range of the experimental conditions and short-wavelength cones contribute to the perception of scene brightness to a limited degree at mesopic light levels.

Comparison of Ocular Pathologies in Vitamin A–Deficient Mice and RPE65 Gene Knockout Mice

RPE65 gene knockout (Rpe65⁻/⁻) mice showed abolished isomerohydrolase activity in the visual cycle and were considered a model for vitamin A deficiency in the retina. The purpose of this study was to compare the retinal phenotypes between vitamin A-deficient (VAD) mice and Rpe65⁻/⁻ mice under normal diet. The VAD mice were fed with a vitamin A-deprived diet after birth. The age-matched control mice and Rpe65⁻/⁻ mice were maintained under normal diet. The structure of photoreceptor outer segment was compared using electron microscopy. Photoreceptor-specific gene expression was determined using real-time RT-PCR. The isomerohydrolase and lecithin-retinol acyltransferase (LRAT) activities were measured using an in vitro enzymatic activity assay. Endogenous retinoid profiles were analyzed by HPLC in mouse eyecup homogenates. Compared to wild-type mice under normal diet, scanning and transmission electron microscopy showed that the outer segments of photoreceptors were disorganized in VAD mice and were not disorganized in Rpe65⁻/⁻ mice, although they were shortened in the latter. VAD mice showed more prominent downregulation of middle wavelength cone opsin, whereas Rpe65⁻/⁻ mice displayed more suppressed expression of short wavelength cone opsin. In vitro enzymatic activity assay and Western blot analysis showed that vitamin A deprivation downregulated LRAT expression and activity in the eyecup, but Rpe65⁻/⁻ mice showed unchanged LRAT expression and activity. The depressed LRAT activity in VAD mice was partially rescued by the intraperitoneal injection of retinoic acid. VAD and Rpe65⁻/⁻ mice are different in cone photoreceptor degeneration, photoreceptor-specific gene regulation, isomerohydrolase activity, endogenous retinoid profile, and LRAT activity.

Temporal frequency and chromatic processing in humans: An fMRI study of the cortical visual areas

Psychophysical sensitivity to isoluminant chromatic modulation declines at temporal frequencies beyond 4 Hz, whereas chromatically opponent cells of the afferent visual pathway (long- to middle-wavelength (L-M) cone-opponent or short-wavelength (S) cone cells) show responses at much higher temporal frequencies, indicating a central limitation in temporal processing capacity. Here, we sought to localize this limit in cortical retinotopic visual areas. We used fMRI to investigate responses of lateral geniculate nucleus and cortical visual areas in humans to isoluminant chromatic modulation as a function of temporal frequency (2-12 Hz). Our results suggest that L-M cone-opponent and S-cone signals are processed in LGN up to 12 Hz. In all visual areas except MT (middle temporal) and V3a, S-cone responses declined steeply with temporal frequency, implying that psychophysical sensitivity loss to blue-yellow modulation might occur early within these areas. While V1 showed robust L-M responses up to 12 Hz, there was a progressive falloff of responses with temporal frequency as information is transferred from V1 to higher areas (V2, V3, and V4), suggesting that, in humans, temporal limitation in perception of red-green chromatic modulation likely results from limited processing capacity of higher ventral extrastriate areas.

Conserved residues in the extracellular loops of short-wavelength cone visual pigments.

The role of the extracellular loop region of a short-wavelength sensitive pigment, Xenopus violet cone opsin, is investigated via computational modeling, mutagenesis, and spectroscopy. The computational models predict a complex H-bonding network that stabilizes and connects the EC2-EC3 loop and the N-terminus. Mutations that are predicted to disrupt the H-bonding network are shown to produce visual pigments that do not stably bind chromophore and exhibit properties of a misfolded protein. The potential role of a disulfide bond between two conserved Cys residues, Cys(105) in TM3 and Cys(182) in EC2, is necessary for proper folding and trafficking in VCOP. Lastly, certain residues in the EC2 loop are predicted to stabilize the formation of two antiparallel β-strands joined by a hairpin turn, which interact with the chromophore via H-bonding or van der Waals interactions. Mutations of conserved residues result in a decrease in the level of chromophore binding. These results demonstrate that the extracellular loops are crucial for the formation of this cone visual pigment. Moreover, there are significant differences in the structure and function of this region in VCOP compared to that in rhodopsin.

Testing a provisional model of scene brightness with and without objects of different colours

A provisional model of brightness perception for illuminated outdoor scenes was recently proposed based upon a combination of photopic and short-wavelength cone spectral sensitivities, where short-wavelength cone sensitivity increases with radiance. An experiment was undertaken to determine whether coloured objects within the illuminated scenes affected overall scene brightness perception and, in so doing, to provide a test of the provisional model. The results suggest that overall scene brightness perceptions are, for the range of light sources and light levels selected, consistent with the provisional model and that scene brightness perception is independent of object colours within the illuminated scenes.

Characterization of a novel large-field cone bipolar cell type in the primate retina: Evidence for selective cone connections

Parallel processing of visual information begins at the first synapse in the retina between the photoreceptors and bipolar cells. Ten bipolar cell types have been previously described in the primate retina: one rod and nine cone bipolar types. In this paper, we describe an 11th type of bipolar cell identified in Golgi-stained macaque retinal whole mount and vertical section. Axonal stratification depth, in addition to dendritic and axonal morphology, distinguished the "giant" cell from all previously well-recognized bipolar cell types. The giant bipolar cell had a very large and sparsely branched dendritic tree and a relatively large axonal arbor that costratified with the DB4 bipolar cell near the center of the inner plexiform layer. The sparseness of the giant bipolar's dendritic arbor indicates that, like the blue cone bipolar, it does not contact all the cones in its dendritic field. Giant cells contacting the same cones as midget bipolar cells, which are known to contact single long-wavelength (L) or medium-wavelength (M) cones, demonstrate that the giant cell does not exclusively contact short-wavelength (S) cones and, therefore, is not a variant of the previously described blue cone bipolar. This conclusion is further supported by measurement of the cone contact spacing for the giant bipolar. The giant cell contacts an average of about half the cones in its dendritic field (mean ± S.D. = 52 ± 17.6%; n = 6), with a range of 27-82%. The dendrites from single or neighboring giant cells that converge onto the same cones suggest that the giant cell may selectively target a subset of cones with a highly variable local density, such as the L or M cones.

Observational learning in rats

Vertebrate ancestors had only cone-like photoreceptors. The duplex retina evolved in jawless vertebrates with the advent of highly photosensitive rod-like photoreceptors. Despite cones being the arbiters of high-resolution color vision, rods emerged as the dominant photoreceptor in mammals during a nocturnal phase early in their evolution. We investigated the evolutionary and developmental origins of rods in two divergent vertebrate retinas. In mice, we discovered genetic and epigenetic vestiges of short-wavelength cones in developing rods, and cell-lineage tracing validated the genesis of rods from S cones. Curiously, rods did not derive from S cones in zebrafish. Our study illuminates several questions regarding the evolution of duplex retina and supports the hypothesis that, in mammals, the S-cone lineage was recruited via the Maf-family transcription factor NRL to augment rod photoreceptors. We propose that this developmental mechanism allowed the adaptive exploitation of scotopic niches during the nocturnal bottleneck early in mammalian evolution.

Morphological changes of short-wavelength cones in the developing S334ter-3 transgenic rat

The S334ter-3 rat is a transgenic model of retinal degeneration (RD) developed to express a rhodopsin mutation similar to that found in human retinitis pigmentosa. Due to this advantage over other models of RD, a few retina transplant studies have been reported on this animal model. Currently, no information is available on cone photoreceptor changes that occur in the S334ter RD model. In this study, we investigated the effect of RD on the morphology, distribution, and synaptic connectivity of short-wavelength cones (S-cones) during development of S334ter-3 rat retinas. At P21 RD retinas, the outer-nuclear layer was significantly narrower, while S-cones showed shortening of their segments and axons compared to control retinas. From P90 onward, S-opsin-immunoreactive cells appeared at the outer margin of the inner-nuclear layer of RD retinas. Double-labelling experiments showed these cells contained recoverin and cone arrestin. Furthermore, ultra-structure study showed that synaptic ribbons are conserved in the S-cone at P180 RD retinas. Although cell density of S-cones significantly dropped after P90, survival rates depended on the retinal region. Overall, the S334ter-3 RD model shows hallmarks of cone remodelling due to photoreceptor degeneration.

Spectral discomfort glare sensitivity investigations

The main concern of car headlamp manufacturers is to provide better visibility. Unfortunately, by increasing the luminous intensity of the headlamp, the risk of increasing discomfort glare for the other road users increases. One possibility to increase visibility and decrease glare could be the selection of a spectral power distribution for the headlamp such that it emits in wavelength regions (if such wavelengths exist) where luminous sensitivity is high, and glare sensitivity is low. For this the spectral discomfort glare sensitivity of humans under low photopic conditions has to be determined. Spectral discomfort glare sensitivity was determined using ten young observers, requesting the observers to select medium glare settings of monochromatic radiations based on the de Boer glare rating scale, both at near-foveal and 10 degrees extra-foveal directions of the 2 degrees diameter glare source. It was found that the spectral discomfort glare sensitivity function could not be described by a simple addition of the photopic spectral luminous efficiency function and the short wavelength cone fundamental, but that the contribution of the chromatic channels of human vision may also have to be considered.

Spectral sensitivity for extrafoveal discomfort glare

Previously published evidence suggests that the discomfort glare response to bright lights has greater short-wavelength spectral sensitivity than implied by the photopic luminous efficiency function, V(λ). The present paper summarizes a series of experiments to characterize spectral sensitivity for discomfort glare from nearly monochromatic light sources presented in the near extrafovea (5° and 10° off-axis). The results are consistent with increased participation in the discomfort glare response from short-wavelength cones and greater short-wavelength sensitivity as eccentricity increases. From the results an empirical family of luminous efficiency functions, V DG(λ), for discomfort glare, is derived. Such data could have implications for specifications of roadway lighting, vehicle headlamps or other light sources that might contribute to discomfort glare.

Neural models and physiological reality

Neural models of retinal processing provide an important tool for analyzing retinal signals and their functional significance. However, it is here argued that in biological reality, retinal connectivity is unlikely to be as specific as ideal neural models might suggest. The retina is thought to provide functionally specific signals, but this specificity is unlikely to be anatomically complete. This is illustrated by examples of cone connectivity to macaque ganglion cells. For example, cells of the magnocellular pathway appear to avoid short-wavelength cone input, so that such input is negligible under normal conditions. However, there is anatomical, physiological, and psychophysical evidence that under special conditions, weak input may be revealed. Second, ideal models of how retinal information is centrally utilized have to take into account the biological reality of retinal signals. The stochastic nature of impulse trains modifies signal-to-noise ratio in unexpected ways. Also, non-linearities in cell responses make, for example, multiplexing of luminance and chromatic signals in the parvocellular pathway impracticable. The purpose of this analysis is to show than ideal neural models must confront an often more complex and nuanced physiological reality.

Functional and Structural Changes in the Retina of Wire-Haired Dachshunds with Early-Onset Cone–Rod Dystrophy

To describe and classify the morphologic changes in a naturally occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate these with earlier described clinical characteristics of the disease in dogs. Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a large pedigree of dogs with early-onset CRD were euthanatized at defined ages to characterize morphologic changes in the disease process. Specimens were examined by light microscopy, including morphometric studies, electron microscopy, and immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC), synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP), and short-wavelength cone opsin (OS) were used for immunohistochemical characterization. The photopic cone-system-derived ERG amplitudes were already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks, the earliest age studied. The outer retina was morphologically most severely affected initially, with a subsequent degeneration of the inner retina. Cone degeneration was more pronounced than rod degeneration in young CRD-affected dogs. There was a marked phenotypic variation based on morphologic findings in the affected dogs. At the earliest time point studied (5-8 weeks) cone photoreceptor and glial cell abnormalities were observed, in accordance with earlier studies based on electrophysiological and clinical findings in which day blindness and abnormal cone ERGs were observed in young affected SWHD puppies. Preliminary genetic studies have indicated an autosomal recessive mode of inheritance for the defect. Through functional and structural characterization, early-onset cone abnormalities were found, consistent with a cone dysplasia at an age when rod structure was normal. Further studies are in progress to identify the gene(s) involved in this retinal disease process. The presently described natural animal model of primary cone dysplasia followed by rod degeneration may provide further insight into the human counterpart. Further studies are needed to ascertain an autosomal recessive mode of inheritance for CRD in the SWHD.

Redundant target effect and the processing of colour and luminance

The redundant target effect is the observation that people typically respond faster to double targets (two targets presented simultaneously) than to either of the targets presented alone. This difference in latency is termed the redundancy gain (RG). Chromatic targets may be accompanied with luminance changes at their onset and offset. We have used a dynamic random luminance modulation technique to mask out luminance components of chromatic signals. Here we report on the presence of a significant RG for visual targets defined by their combined luminance and chromatic components as well as their chromatic content in isolation. Reaction times were measured to the onset of three classes of stimuli, namely, Long- and Short-wavelength cone sensitive (L- and S-cone) targets matched for saliency as well as luminance-defined targets. Analysis of the cumulative distributions of reaction time data showed that a neural coactivation model could fit the experimental data for chromatic targets only. When a luminance component is present, the reaction time data can be explained by a probability summation account also known as the race model.

Perception Matches Selectivity in the Human Anterior Color Center

Human ventral cortex contains at least two visual areas selective for color [1]: a posterior center in the lingual gyrus labeled V4 [2-4], V8 [5], or VO-1 [6] and an anterior center in the medial fusiform that has been labeled V4alpha[3, 4]. We examined the properties of the anterior color center using electrical recording and electrical stimulation in a subject with an electrode implanted over the anterior color center, as determined with BOLD fMRI in the same subject. Presentation of visual stimuli evoked local field potentials from the electrode. Consistent with fMRI, the potentials were larger for chromatic than achromatic stimuli. The potentials differed depending on stimulus color, with blue-purple colors evoking the largest response. The spatial receptive field of the electrode was central/parafoveal with a contralateral bias. In the absence of a visual stimulus, electrical stimulation of the electrode produced an artificial visual percept of a blue-purple color near the center of gaze. These results provide direct evidence of a tight link between selectivity and perception in ventral temporal cortex. Electrical stimulation of the anterior color center is sufficient to produce the conscious percept of a color whose identity is determined by the selectivity of the stimulated neurons.

NeuroD1 Regulates Expression of Thyroid Hormone Receptor β2 and Cone Opsins in the Developing Mouse Retina

The correct patterning of opsin expression in cone photoreceptors is critical for normal color vision. Thyroid hormone, and one of its receptors [thyroid hormone receptor beta2 (TRbeta2)], is an important regulator of opsin expression during cone photoreceptor development. Mice have two genes, encoding medium-wavelength (M) and short-wavelength (S) cone opsins. Targeted deletion of TRbeta2 leads to a uniform expression of S-opsin in all cone photoreceptors and a loss of M-opsin. The control of expression of TRbeta2 is therefore central to cone differentiation, yet there is little known about its regulation in the retina. We now report that the proneural bHLH (basic helix-loop-helix) transcription factor, NeuroD1, is necessary for sustained expression of TRbeta2 in immature cone photoreceptors. Mice deficient in NeuroD1 develop an opsin phenotype virtually identical with that of TRbeta2-deficient mice: all cones express S-opsin, and none expresses M-opsin. The introduction of NeuroD1 into embryonic retinal explants from NeuroD1-/- mice restores TRbeta2 expression. NeuroD1 binds an E-box in the intron control region of the TRbeta2 gene that mediates cone-specific expression, suggesting that NeuroD1 is a critical contributory factor to the expression of TRbeta2 in cones. These results thus connect the proneural pathway with opsin selection to ensure correct cone patterning during retinal development.

Bio‐avalibale zinc in the outer segments of short wavelength cones

Abstract Purpose: Zinc has been postulated to play a role in both normal and degenerative processes in the retina. Often these processes require zinc that is tightly bound to enzymes. However, new evidences indicate that the presence of bio‐available zinc is a better indicator for the involvemnt of zinc in retinal fuctions. Using autometallography on sectioned tissues suggested that bio‐available zinc is absent in photoreceptor outer segments. The purpose of this study was to re‐examine this observation using a zinc selective fluorescence probe and freshly dissected, flat mounted retinae . Methods: Following deep anesthesia and decapitation, dark‐adapted retinae were immediately dissected from rat, goldfish and chicken eyes and flat mounted with the photoreceptor up. The retinae were immediately labeled with the zinc‐specific fluorescent probe ZP1 (Neurobiotex, USA). Readily releasable zinc was visualized using fluorescent and confocal microscopy. Results: Only a subset of photoreceptor outer segments were labeled by ZP1 in rat retinae (>0.5 %). This labelling was localized to a subset of the cones. The cone localization of this labeling was confirmed by using goldfish retinae where the cones are readily distinguishable from rods morphologically. To identify the subtype of zinc postive cones we labeled chicken retinae where the characteristic oil droplets within the cones identify their sub‐type. Here zinc appeared to be localized to short wavelength cone outer segments. Conclusions: This is the first demonstration that bio‐available zinc is present in photoreceptor outer segments. The specific localization to short wavelength cones suggest that zinc plays a selective role in visual processing of short wavelength light.

Photoreceptor organization and rhythmic phagocytosis in the nile rat Arvicanthis ansorgei: a novel diurnal rodent model for the study of cone pathophysiology.

To characterize rod and cone distribution, organization, and phagocytosis in the diurnal mouse-like rodent Arvicanthis ansorgei. Retinas of adult A. ansorgei were processed for histology, electron microscopy and immunohistochemistry using rod- and mouse cone-specific antibodies. For phagocytosis studies, retinas were sampled every 3 hours under a 12-hour light-dark cycle and processed for double-label immunohistochemistry. The number of phagosomes in the retinal pigmented epithelium were quantified with a morphometric system. A. ansorgei retinas were composed of 33% cones and 67% rods, approximately 10 times more cones than mice and rats. Cones were arranged in two cell layers at the scleral surface, distributed uniformly across the entire retina. Cone arrestin was distributed throughout the dark-adapted cones, from outer segments to synapses, whereas short- and mid-wavelength cone opsins were restricted to outer segments. Short-wavelength cone density was mapped in wholemounted retinas, in a significantly higher number in the central region. Rhodopsin immunopositive (rod) phagosomes showed a small peak late in the dark phase, then a large burst 1 to 2 hours after light onset, after decreasing to low baseline levels by 12 AM. Mid-wavelength cone opsin immunopositive (cone) phagosomes were 10 times less numerous than rods, and demonstrated a broad peak 1 to 2 hours after light onset. The diurnal rodent A. ansorgei possesses a large number of cones, organized in a strict anatomic array. Rod and cone outer segment phagocytosis and shedding can be monitored simultaneously and show similar profiles but different amplitudes. This species may constitute a valuable novel animal model for investigating cone pathophysiology.

Visual function and dysfunction in early and late age-related maculopathy

Late age-related maculopathy (ARM) is responsible for the majority of blind registrations in the Western world among persons over 50 years of age. It has devastating effects on quality of life and independence and is becoming a major public health concern. Current treatment options are limited and most aim to slow progression rather than restore vision; therefore, early detection to identify those patients most suitable for these interventions is essential. In this work, we review the literature encompassing the investigation of visual function in ARM in order to highlight those visual function parameters which are affected very early in the disease process. We pay particular attention to measures of acuity, contrast sensitivity (CS), cone function, electrophysiology, visual adaptation, central visual field sensitivity and metamorphopsia. We also consider the impact of bilateral late ARM on visual function as well as the relationship between measures of vision function and self-reported visual functioning. Much interest has centred on the identification of functional changes which may predict progression to neovascular disease; therefore, we outline the longitudinal studies, which to date have reported dark-adaptation time, short-wavelength cone sensitivity, colour-match area effect, dark-adapted foveal sensitivity, foveal flicker sensitivity, slow recovery from glare and slower foveal electroretinogram implicit time as functional risk factors for the development of neovascular disease. Despite progress in this area, we emphasise the need for longitudinal studies designed in light of developments in disease classification and retinal imaging, which would ensure the correct classification of cases and controls, and provide increased understanding of the natural course and progression of the disease and further elucidate the structure-function relationships in this devastating disorder.

Functional observations in vitamin A deficiency: diagnosis and time course of recovery

To describe the effects of vitamin A deficiency (VAD) on retinal function and the subsequent recovery following treatment in three patients with systemic conditions (two with Crohn disease; one secondary to IgE syndrome). Electrophysiological testing (including pattern electroretinogram, PERG; electroretinogram, ERG; visual-evoked potential) established the diagnosis of VAD. Repeat testing was carried out in two patients to monitor the time course of recovery following intramuscular vitamin A injection. The third patient had repeat recordings following 13 months of oral supplementation. All three patients initially displayed a characteristic absence of rod function associated with VAD. In addition, delayed and reduced amplitude cone ERGs, loss of short wavelength cone (S-cone) function and subnormal macular function were observed in two patients. Restoration of rod and generalised cone function was rapid in the two patients who received intramuscular injection, with normalisation of some electrophysiological responses after only 3 days. Normal S-cone amplitudes and cone latencies were reached within 12 days of vitamin A injection. Macular function returned to within normal limits by 12 days postinjection in one patient, but remained mildly subnormal in the second patient. Full recovery was present after 13 months oral supplementation in the third patient. Novel observations regarding dark-adapted cone function, S-cone function, and PERG are presented. The differences between the effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptor classes. The importance of rapidly and accurately diagnosing VAD, a treatable condition, is noted.

Short-Wavelength Content of LED Headlamps and Discomfort Glare

This study evaluated the effect of short-wavelength content of headlamps on discomfort glare, in order to provide guidance regarding spectral compositions that would minimize driver complaints. Three light-emitting diode (LED) headlamps were tested (with correlated color temperatures of 4000, 4800, and 6600 K), as well as a tungsten-halogen headlamp and a high-intensity discharge (HID) headlamp. Subjects, seated in a stationary vehicle, rated discomfort from brief presentations of stimuli that produced illuminances of 0.25, 0.5, and 1 lx.As predicted in our previous analytical study, we found that—when they appear bluer than current tungsten-halogen or HID headlamps—LED headlamps tend to produce more discomfort glare. The effect is probably due to the color appearance of the LED lamps used in this study rather than to any inherent characteristic of LED sources, and it could probably be altered or reversed with different sources. For the data reported here, ratings of discomfort glare were linearly related to the amount of short-wavelength content in the light output as weighted by the spectral sensitivity of the short-wavelength cone photoreceptors. Thus, the present study provides support for the hypothesis that the short-wavelength content of the headlamp output could be used heuristically to select colors of headlamps to minimize driver complaints about glare.