S-cone Responses Research Articles

Age-dependencies of the electroretinogram in healthy subjects.

The purpose of this study was to evaluate the age-dependency of amplitudes and implicit times in the electroretinograms (ERGs) of healthy individuals and provide clinicians and researchers with a reference for a variety of stimulus paradigms. Full-field electroretinography was conducted on 73 healthy participants aged 14-73 using an extended ISCEV standard protocol that included an additional 9Hz flicker stimulus for assessing rod function and special paradigms for isolated On-Off and S-cone responses. Correlation coefficients and best-fit regression models for each parameter's age-dependency were calculated. Dark-adapted ERGs, in particular, displayed notable age-related alterations. The attenuation and delay of the b-wave with higher age were most significant in the dark-adapted, rod-driven 0.001cds/m2 flash ERG. The age-dependent reduction of the a-wave amplitude was strongest in the standard dark-adapted 3cds/m2 flash condition. Cone-driven, light-adapted responses to either flash or flicker stimuli displayed comparatively small alterations at higher age. S-cone function tended to diminish at an early age, but the effect was not significant in the whole population. The results suggest that rod and cone function decline at different rates with age, with rods being generally more affected by aging. Nonetheless, response amplitudes displayed a wide variability across the whole sample.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

A Novel Autosomal Recessive Variant of the NRL Gene Causing Enhanced S-Cone Syndrome: A Morpho-Functional Analysis of Two Unrelated Pediatric Patients.

Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS.

Intraperitoneal chromophore injections delay early-onset and rapid retinal cone degeneration in a mouse model of Leber congenital amaurosis

Highly expressed in the retinal pigment epithelium (RPE), the RPE-specific 65-kDa (RPE65) enzyme is indispensable to generate 11-cis-retinal (11cRAL), a chromophore for rhodopsin and cone photopigments. RPE65 deficiency can lead to Leber congenital amaurosis type 2 (LCA2), in which the isomerization of photobleached all-trans-retinal into photosensitive 11cRAL is blocked, ultimately causing severe retinal dysfunction and degeneration. The related mouse models, which are constructed through gene knockout or caused by spontaneous mutations, morphologically present with early-onset and rapid retinal cone cells degeneration, including loss of short-wavelength-sensitive cone opsins (S-opsins) and mislocalization of medium-wavelength-sensitive cone opsins (M-opsins). Studies have shown that routine Rpe65 gene replacement therapy, mediated by an adeno-associated virus (AAV) vector, can restore RPE65 protein. However, AAV transfection and Rpe65 transgene expression require at least one to two weeks, and the treatment cannot fully block the early-onset cone degeneration. To determine the feasibility of delaying cone degeneration before gene therapy, we investigated the impact of 11cRAL treatment in an early-age LCA2 retinal degeneration 12 (rd12) mouse model. Similar to human patients, the mouse model carries a spontaneous mutation in the Rpe65 gene, which results in disrupted endogenous 11cRAL regeneration. We found that RPE65 deficiency did not notably affect rodent retinal vessels. Under red light illumination, the rd12 mice were intraperitoneally injected with exogenous 11cRAL from postnatal day (P) 14 to P21. Three days after the last injection, a notable recovery of retinal function was observed using scotopic and photopic electroretinograms. Using optical coherence tomography and histological analyses of the deficient retinas, we found changes in the thickness of the photoreceptor outer segment (OS); this change could be rescued by early 11cRAL treatment. In addition, the treatment notably preserved M- and S-opsins, both of which maintained appropriate localization inside cone cells, as shown by the wild-type mice. In contrast, the age-matched untreated rd12 mice were characterized by retinal S-opsin loss and M-opsin mislocalization from the photoreceptor OS to the inner segment, outer nuclear layer, or outer plexiform layer. Notably, 11cRAL treatment could not maintain retinal function for a long time. Ten days after the last injection, the rod and M-cone electroretinograms significantly decreased, and S-cone responses almost extinguished. Our findings suggest that early 11cRAL treatment is useful for restoring retinal function and rescuing morphology in the rd12 mouse model, and the early-onset and rapid cone degeneration can be delayed before gene therapy.

A modified silent substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.

A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using silent substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. Three normal adult purpose-bred beagles (2 females and 1 male). Dogs were dark-adapted for 1hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25mcg/kg, butorphanol 0.1mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12Hz), L/M-cone responses peaked at high frequency (32-38Hz), and S-cone responses peaked at low frequency (4-12Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P<.001). We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.

Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging.

Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise &lt;10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400-450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.

Retinal Photoreceptor Functions Are Compromised in Patients With Resistance to Thyroid Hormone Syndrome (RTHβ).

In animal models, disruption of thyroid hormone (TH) receptor-β (TRβ) reduces the long/medium wavelength (L/M) and increases the short-wavelength (S) cones. Retinal photoreceptor (RP) functions are unknown in patients with resistance to TH syndrome (RTHβ) with dominant-negative TRβ mutations. To investigate RP functions in RTHβ. Case-control study involving 27 RTHβ patients and 31 age/sex-matched controls, conducted in two tertiary referral centers in Italy. Color vision sensitivity assessed by Farnsworth; central macular thickness (CMT) of the outer retinal layer measured by spectral-domain optical coherence tomography; and retinal function tested by full-field electroretinogram (ERG) and S-cone ERG. Color sensitivity was worse in RTHβ patients than controls (P = 0.002). CMT was overlapping between the study groups but directly correlated with sex hormone-binding globuline levels in RTHβ. We found a significant reduction in amplitude of the cone (P = 0.024) and of the rod response (P = 0.006) in the ERG of RTHβ patients compared with controls. The response of the L/M cones measured by a specialized ERG test was lower in RTHβ than controls (P = 0.027), whereas no differences were found in the S-cone response. No correlations were found between TH levels, total error score, or electrophysiological results. Furthermore, no differences were found between patients with maternal or de novo/paternal inheritance. We report, to our knowledge, the first in vivo evidence of functional defects of RP in RTHβ. These changes occur independently of endogenous TH levels or the prenatal exposure to high or normal maternal TH.

Color constancy of color-deficient observers under illuminations defined by individual color discrimination ellipsoids.

We explored the color constancy mechanisms of color-deficient observers under red, green, blue, and yellow illuminations. The red and green illuminations were defined individually by the longer axis of the color discrimination ellipsoid measured by the Cambridge Colour Test. Four dichromats (3 protanopes and 1 deuteranope), two anomalous trichromats (2 deuteranomalous observers), and five color-normal observers were asked to complete the color constancy task by making a simultaneous paper match under asymmetrical illuminations in haploscopic view on a monitor. The von Kries adaptation model was applied to estimate the cone responses. The model fits showed that for all color-deficient observers under all illuminations, the adjustment of the S-cone response or blue-yellow chromatically opponent responses modeled with the simple assumption of cone deletion in a certain type (S-M, S-L or S-(L+M)) was consistent with the principle of the von Kries model. The degree of adaptation was similar to that of color-normal observers. The results indicate that the color constancy of color-deficient observers is mediated by the simplified blue-yellow color system with a von Kries-type adaptation effect, even in the case of brightness match, as well as by a possible cone-level adaptation to the S-cone when the illumination produces a strong S-cone stimulation, such as blue illumination.

Do S cones contribute to color-motion feature binding?

Wu et al. [Nature 429, 262 (2004)] describe a visual illusion in which color and motion are incorrectly bound: green dots moving downward and red dots moving upward are seen as green dots going up and red dots going down. The present study determined whether S cones contribute to color-motion feature-binding errors, in order to assess the neural representation of color at the level of binding. The specific experimental question is whether binding errors depend on S-cone responses from the objects perceived to have an illusory direction of motion. Alternatively, only L and M cones may determine the neural representation of color that regulates color-motion feature binding. In two experiments, the chromatic difference was manipulated between central objects, which induce color-motion binding errors, and peripheral objects, where color-motion binding errors occur. The chromaticity difference was varied along only the L/M-cone axis or only the S-cone axis. As in Wu et al. [Nature 429, 262 (2004)], color-motion binding was frequently observed in the periphery when there were no central versus peripheral chromatic differences. Further, the results showed that the frequency of color-motion binding errors in the periphery depended on the difference in S-cone excitation between center and periphery, thereby demonstrating that the neural representation of color at the level of feature binding depends on signals from not only L and M cones but also S cones.

Color signals through dorsal and ventral visual pathways

Explanations for color phenomena are often sought in the retina, lateral geniculate nucleus, and V1, yet it is becoming increasingly clear that a complete account will take us further along the visual-processing pathway. Working out which areas are involved is not trivial. Responses to S-cone activation are often assumed to indicate that an area or neuron is involved in color perception. However, work tracing S-cone signals into extrastriate cortex has challenged this assumption: S-cone responses have been found in brain regions, such as the middle temporal (MT) motion area, not thought to play a major role in color perception. Here, we review the processing of S-cone signals across cortex and present original data on S-cone responses measured with fMRI in alert macaque, focusing on one area in which S-cone signals seem likely to contribute to color (V4/posterior inferior temporal cortex) and on one area in which S signals are unlikely to play a role in color (MT). We advance a hypothesis that the S-cone signals in color-computing areas are required to achieve a balanced neural representation of perceptual color space, whereas those in noncolor-areas provide a cue to illumination (not luminance) and confer sensitivity to the chromatic contrast generated by natural daylight (shadows, illuminated by ambient sky, surrounded by direct sunlight). This sensitivity would facilitate the extraction of shape-from-shadow signals to benefit global scene analysis and motion perception.

Color coding in the cortex: a modified approach to bottom-up visual attention

Itti and Koch's (Vision Research 40:1489-1506, 2000) saliency-based visual attention model is a broadly accepted model that describes how attention processes are deployed in the visual cortex in a pure bottom-up strategy. This work complements their model by modifying the color feature calculation. Evidence suggests that S-cone responses are elicited in the same spatial distribution and have the same sign as responses to M-cone stimuli; these cells are tentatively referred to as red-cyan. For other cells, the S-cone input seems to be aligned with the L-cone input; these cells might be green-magenta cells. To model red-cyan and green-magenta double-opponent cells, we implement a center-surround difference approach of the aforementioned model. The resulting color maps elicited enhanced responses to color salient stimuli when compared to the classic ones at high statistical significance levels. We also show that the modified model improves the prediction of locations attended by human viewers.

Aging of human short-wave cone pathways.

The retinal image is sampled concurrently, and largely independently, by three physiologically and anatomically distinct pathways, each with separate ON and OFF subdivisions. The retinal circuitry giving rise to an ON pathway receiving input from the short-wave-sensitive (S) cones is well understood, but the S-cone OFF circuitry is more controversial. Here, we characterize the temporal properties of putative S-cone ON and OFF pathways in younger and older observers by measuring thresholds for stimuli that produce increases or decreases in S-cone stimulation, while the middle- and long-wave-sensitive cones are unmodulated. We characterize the data in terms of an impulse response function, the theoretical response to a flash of infinitely short duration, from which the response to any temporally varying stimulus may be predicted. Results show that the S-cone response to increments is faster than to decrements, but this difference is significantly greater for older individuals. The impulse response function amplitudes for increment and decrement responses are highly correlated across individuals, whereas the timing is not. This strongly suggests that the amplitude is controlled by neural circuitry that is common to S-cone ON and OFF responses (photoreceptors), whereas the timing is controlled by separate postreceptoral pathways. The slower response of the putative OFF pathway is ascribed to different retinal circuitry, possibly attributable to a sign-inverting amacrine cell not present in the ON pathway. It is significant that this pathway is affected selectively in the elderly by becoming slower, whereas the temporal properties of the S-cone ON response are stable across the life span of an individual.

Functional Topography of Rod and Cone Photoreceptors in Macaque Retina Determined by Retinal Densitometry

The purpose of this study is to determine the topography of bleaching in rods, middle/long-wavelength (M/L) and short-wavelength (S) cones in the macaque retina by using a modified retinal densitometry technique. A modified commercial digital fundus camera system was used to measure continuously the intensity of the light reflectance during bleaching with band pass lights in the ocular fundus of three adult Rhesus monkeys (Macaca mulatta) under general anesthesia. The topography of bleaching in rods, M/L-, and S-cones was obtained separately by considering the characteristic time course of the reflectance changes, depending on the wavelengths of light and retinal locations. The distribution of M/L-cones response had a steep peak at the foveal center and was elongated horizontally. The distribution of rod responses was minimum at the foveal center and maximum along a circular region at the eccentricity of the optic disc. The distribution of S-cone responses was highest at the fovea and was excavated centrally. There was a circular region with the maximal responses at 0.38 to 1.0 degrees from the foveal center. With the current imaging technique, not only the steep peak of the M/L-cone responses at the fovea, but the ring-shaped distribution of rod responses in the periphery and the central reduction of S-cone response could be determined with good resolution.

Reduced L- and M- and increased S-cone functions in an infant with thyroid hormone resistance due to mutations in the THRβ2 gene

Background: To document an infant with a cone photoreceptor disorder associated with severe thyroid hormone resistance due to compound heterozygosity in the thyroid hormone receptor beta 2 (TRβ2) encoding gene THRβ2.Materials and methods: Cone photoreceptor function was assessed using standard electroretinography (ERG) including colored flashes. We PCR-amplified and sequenced exons 8-10 of the THRβ2 gene. We cloned and sequenced a genomic segment (exons 9-10) of the THRβ2 gene to confirm a compound heterozygote mutation. We investigated whether mutations in the (OPN1LW-OPN1MW) gene array were responsible for the phenotype.Results: ERG testing showed a normal scotopic response and severely reduced photopic response. Spectral testing showed a small amplitude b-wave to a red flash and a larger amplitude b-wave to the blue flash. Molecular analysis revealed this child was a compound heterozygote for p.R338W and p.R429W mutations in exons 9 and 10 of the THRβ2 gene. These two mutations lie within the ligand-binding domain that is known to selectively inhibit Trβ2 binding as homodimers to the thyroid hormone receptor response elements (TREs). No mutations were found within the OPN1LW and OPN1MW genes or the locus control region that regulates expression of these opsin genes.Conclusion: We document a congenital disorder of cone function characterized by severely reduced L- and M-cone responses and increased S-cone responses caused by deleterious mutations in the THRβ2 gene in thyroid resistant patients. Thyroid hormone, via TRβ2, is critical for determining cone-type differentiation in humans.

Electroretinographic evaluation of the retinal S-cone system

The aim of this study was to differentiate S-cone responses from other retinal activities using various recording conditions and to optimize these recording conditions for clinical diagnostics. S-cone responses to blue stimuli (449 nm) were studied in 20 healthy subjects and four patients with enhanced S-cone syndrome. The time-integrated luminance of the stimulus varied from 0.008 to 1.0 cd s/m2. Three isoluminant backgrounds were used (100 ph cd/m2=40 sc cd/m2): amber (594 nm), green (513 nm), and red (635 nm). With low flash strengths (from 0.008 to 0.032 cd s/m2), the S-cone response appeared as a single positive peak, while with higher strengths (≥0.064 cd s/m2), it appeared as a second peak that followed the L-cone and M-cone components. With a further increase in flash strength (≥0.25 cd s/m2), the S-cone response interfered with the i-wave of the L-cone and M-cone systems. The wavelength and luminance of the background influenced the suppression of the rods, as well as the L-cone- and M-cone-system activities. The S-cone response was measurable in the presence of the amber and green backgrounds, but its amplitude was higher if a strong red background was used. Thus, the function of the retinal S-cone system can be measured if possible interference from other retinal sources can be minimized by the appropriate combination of stimulus and background parameters.

Rod Phosphodiesterase-6 (PDE6) Catalytic Subunits Restore Cone Function in a Mouse Model Lacking Cone PDE6 Catalytic Subunit

Rod and cone photoreceptor neurons utilize discrete PDE6 enzymes that are crucial for phototransduction. Rod PDE6 is composed of heterodimeric catalytic subunits (αβ), while the catalytic core of cone PDE6 (α') is a homodimer. It is not known if variations between PDE6 subunits preclude rod PDE6 catalytic subunits from coupling to the cone phototransduction pathway. To study this issue, we generated a cone-dominated mouse model lacking cone PDE6 (Nrl(-/-) cpfl1). In this animal model, using several independent experimental approaches, we demonstrated the expression of rod PDE6 (αβ) and the absence of cone PDE6 (α') catalytic subunits. The rod PDE6 enzyme expressed in cone cells is active and contributes to the hydrolysis of cGMP in response to light. In addition, rod PDE6 expressed in cone cells couples to the light signaling pathway to produce S-cone responses. However, S-cone responses and light-dependent cGMP hydrolysis were eliminated when the β-subunit of rod PDE6 was removed (Nrl(-/-) cpfl1 rd). We conclude that either rod or cone PDE6 can effectively couple to the cone phototransduction pathway to mediate visual signaling. Interestingly, we also found that functional PDE6 is required for trafficking of M-opsin to cone outer segments.

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.

Silent Substitution Stimulation of S-cone Pathway and L- and M-cone Pathway in Glaucoma

The study aimed for objective detection of primary open-angle glaucoma with selective color channel stimulation based on the silent substitution technique. In addition, an objective was analysis of the characteristics of individual color channels based on visual evoked potentials. Visual evoked potentials were recorded in 141 subjects (39 patients with glaucoma, 71 healthy subjects, and 31 age-matched healthy subjects) with two scalp electrodes after cone-specific flash stimulation. Silent substitution stimulation was presented with a 30-in. liquid crystal display. Separate responses were obtained for short-, medium-, and long-wavelength-sensitive cones. Age-matched subgroups were used to compare patients with glaucoma and healthy subjects. The S-cone responses of age-matched healthy subjects had significantly different slopes for the first positive wave, compared with the responses of patients with moderate glaucoma. This difference was not observed in the L- and M-cone responses. Distinct changes in the S-cone response profiles were observed with increasing severity of glaucoma. Patients with severe glaucomatous damage were recognizable by the altered profiles of their visual evoked potentials. Healthy subjects showed significant differences between color channels. Glaucoma and its severity were objectively detected by using the silent substitution technique. The stimulation technique and signal analysis enabled assessment of the visual evoked potentials of individual color channels.

The S-cone contribution to luminance depends on the M- and L-cone adaptation levels: Silent surrounds?

Under dim background conditions, the S-cones make little or no contribution to luminance (A. Eisner & D. I. MacLeod, 1980; W. Verdon & A. J. Adams, 1987), yet under conditions of intense long-wavelength adaptation, a small but robust contribution to luminance--as defined by heterochromatic flicker photometry (A. Stockman, D. I. MacLeod, & D. D. DePriest, 1987, 1991) or motion (J. Lee & C. F. Stromeyer, 1989)--can be found. Here, by using selective adaptation and/or tritanopic metamers to isolate the S-cone response, we investigate the dependence of the S-cone luminance input on changes in background wavelength and radiance. Interestingly, the S-cone luminance input disappears completely when no adapting background is present, even though the same S-cone stimulus makes a clear contribution to luminance when a background is present. The dependence of the S-cone luminance input on the wavelength and radiance of the adapting background is surprising. We find that the S-cone signal can be measured on fields of 491 nm and longer wavelengths that exceed a criterion background radiance. These criterion radiances roughly follow an L + M spectral sensitivity, which suggests that the S-cone luminance input is silent unless the L- and M-cones are excited above a certain level. We hypothesize that the L + M cone signals produced by the steady adapting backgrounds somehow "gate" the S-cone luminance signals, perhaps by being modulated by them.

Atypical Mild Enhanced S-Cone Syndrome with Novel Compound Heterozygosity of the NR2E3 Gene

To report mild enhanced s-cone syndrome (ESCS) associated with a novel heterozygous mutation of the NR2E3 gene. Observational case report. Clinical examination, optical coherence tomography (OCT), electroretinography (ERG), genetic analysis, and protein homology modeling. Examination of a 9-year-old girl with acute visual loss of the left eye showed visual acuity of 20/30 in the right eye and 20/200 in the left eye; OCT revealed a choroidal neovascular membrane (CNVM) in the left fovea and cystic maculopathy in the right eye. Full-field ERG showed supranormal s-cone responses, reduced rod response, and characteristic ESCS waveform in photopic cone response but not in scotopic bright-flash response. Sequence analysis revealed heterozygous mutations in the NR2E3 gene, c.767C-->T yielding a substitution p.Ala256Val, and a mutation in the splice site before exon 2, c.119-2 A-->C. The p.Ala256Val mutation affects the ligand binding domain of the NR2E3 nuclear receptor only, resulting in modestly impaired ESCS ERG results.