Middle-wavelength Sensitive Cones Research Articles

Invited Session III: Diversity in chromatic processing across the animal kingdom: Comparative connectomics reveals noncanonical wiring for color vision in human foveal retina.

The Old World macaque monkey and New World common marmoset provide fundamental models for human visual processing, yet the human ancestral lineage diverged from these monkey lineages over 25 Mya. We therefore asked whether fine-scale synaptic wiring in the nervous system is preserved across these three primate families, despite long periods of independent evolution. We applied connectomic electron microscopy to the specialized foveal retina where circuits for highest acuity and color vision reside. Synaptic motifs arising from the cone photoreceptor type sensitive to short (S) wavelengths and associated with "blue-yellow" (S-ON and S-OFF) color-coding circuitry were reconstructed. We found that distinctive circuitry arises from S cones for each of the three species. The S cones contacted neighboring L and M (long- and middle-wavelength sensitive) cones in humans, but such contacts were rare or absent in macaques and marmosets. We discovered a major S-OFF pathway in the human retina and established its absence in marmosets. Further, the S-ON and S-OFF chromatic pathways make excitatory-type synaptic contacts with L and M cone types in humans, but not in macaques or marmosets. Our results predict that early-stage chromatic signals are distinct in the human retina and imply that solving the human connectome at the nanoscale level of synaptic wiring will be critical for fully understanding the neural basis of human color vision.

Comparative connectomics reveals noncanonical wiring for color vision in human foveal retina

The Old World macaque monkey and New World common marmoset provide fundamental models for human visual processing, yet the human ancestral lineage diverged from these monkey lineages over 25 Mya. We therefore asked whether fine-scale synaptic wiring in the nervous system is preserved across these three primate families, despite long periods of independent evolution. We applied connectomic electron microscopy to the specialized foveal retina where circuits for highest acuity and color vision reside. Synaptic motifs arising from the cone photoreceptor type sensitive to short (S) wavelengths and associated with "blue-yellow" (S-ON and S-OFF) color-coding circuitry were reconstructed. We found that distinctive circuitry arises from S cones for each of the three species. The S cones contacted neighboring L and M (long- and middle-wavelength sensitive) cones in humans, but such contacts were rare or absent in macaques and marmosets. We discovered a major S-OFF pathway in the human retina and established its absence in marmosets. Further, the S-ON and S-OFF chromatic pathways make excitatory-type synaptic contacts with L and M cone types in humans, but not in macaques or marmosets. Our results predict that early-stage chromatic signals are distinct in the human retina and imply that solving the human connectome at the nanoscale level of synaptic wiring will be critical for fully understanding the neural basis of human color vision.

Novel OPN1LW/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction.

Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3–5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.

Appearance of special colors in deuteranomalous trichromacy

Deuteranomalous color matching behavior is different from normal because the middle-wavelength sensitive cones contain an abnormal Lʹ pigment instead of the M pigment of the normal observer. However, there is growing evidence that deuteranomalous color experience is not very different from that of normal trichromats. Here, normal and deuteranomalous observers chose monochromatic unique yellow lights. They also chose broadband lights, displayed on a computer monitor, that corresponded to eight special colors: the Hering unique hues (red, yellow, green, blue), and binary colors perceptually midway between them (orange, lime, cyan, purple). Deuteranomalous monochromatic unique yellow was shifted towards red, but all the broadband special color selections were physically similar for normal and deuteranomalous observers. Deuteranomalous special colors, including monochromatic unique yellow, were similar to those of normal observers when expressed in a color-opponent chromaticity diagram based on their own visual pigments, but only if (1) color-opponent responses were normalized to white, and (2) the deuteranomalous diagram was expanded along the r – g dimension to compensate for the reduced difference between deuteranomalous L- and Lʹ-cone photopigments. Particularly, deuteranomalous observers did not choose binary colors with extra r – g impact to overcome their insensitivity along the r – g dimension. This result can only be compatible with the known abnormality of the deuteranomalous Lʹ photopigment if deuteranomalous observers adjust their perceptual representation of colors to compensate for their color vision deficiency.

The spectral identity of foveal cones is preserved in hue perception.

Organisms are faced with the challenge of making inferences about the physical world from incomplete incoming sensory information. One strategy to combat ambiguity in this process is to combine new information with prior experiences. We investigated the strategy of combining these information sources in color vision. Single cones in human subjects were stimulated and the associated percepts were recorded. Subjects rated each flash for brightness, hue, and saturation. Brightness ratings were proportional to stimulus intensity. Saturation was independent of intensity, but varied between cones. Hue, in contrast, was assigned in a stereotyped manner that was predicted by cone type. These experiments revealed that, near the fovea, long and middle wavelength sensitive cones produce sensations that can be reliably distinguished on the basis of hue, but not saturation or brightness. Taken together, these observations implicate the high-resolution, color-opponent parvocellular pathway in this low-level visual task.

Spectral and spatial selectivity of luminance vision in reef fish.

Luminance vision has high spatial resolution and is used for form vision and texture discrimination. In humans, birds and bees luminance channel is spectrally selective—it depends on the signals of the long-wavelength sensitive photoreceptors (bees) or on the sum of long- and middle-wavelength sensitive cones (humans), but not on the signal of the short-wavelength sensitive (blue) photoreceptors. The reasons of such selectivity are not fully understood. The aim of this study is to reveal the inputs of cone signals to high resolution luminance vision in reef fish. Sixteen freshly caught damselfish, Pomacentrus amboinensis, were trained to discriminate stimuli differing either in their color or in their fine patterns (stripes vs. cheques). Three colors (“bright green”, “dark green” and “blue”) were used to create two sets of color and two sets of pattern stimuli. The “bright green” and “dark green” were similar in their chromatic properties for fish, but differed in their lightness; the “dark green” differed from “blue” in the signal for the blue cone, but yielded similar signals in the long-wavelength and middle-wavelength cones. Fish easily learned to discriminate “bright green” from “dark green” and “dark green” from “blue” stimuli. Fish also could discriminate the fine patterns created from “dark green” and “bright green”. However, fish failed to discriminate fine patterns created from “blue” and “dark green” colors, i.e., the colors that provided contrast for the blue-sensitive photoreceptor, but not for the long-wavelength sensitive one. High resolution luminance vision in damselfish, Pomacentrus amboinensis, does not have input from the blue-sensitive cone, which may indicate that the spectral selectivity of luminance channel is a general feature of visual processing in both aquatic and terrestrial animals.

Kainate receptors: on the dark side

Synaptic glutamate receptors can be divided into metabotropic receptors, an eight-member GPCR family, and ionotropic glutamate receptors, a three-member family of NMDA, kainate, and AMPA tetrameric receptors. The most neglected are the five subunit (GluK1–5) kainate receptors, often either lumped with the AMPA receptors because of pharmacological ambiguity or relegated to the role of synaptic modulators (Lerma, 2003). In the paper by Lindstrom et al. (2014) published in this issue of The Journal of Physiology, not only is the kainate receptor shown to be central to synaptic communication, but subtypes of the receptor are localized to specific cell types in order to convey unique signals across the synapse. Nature demonstrates that receptor subtypes really matter and that neurons segregate proteins to multiplex information across labelled lines using binding and kinetics, not just hard wiring. The first synapse in retina is perhaps the ideal model for exploring the implications of receptor diversity. Photoreceptors release glutamate that is detected by three groups of cells. One, the On bipolar cell, uses the mGluR6 coupled with TRPM1 to invert the sign of the synapse – transforming photoreceptor excitation in the dark into a depolarizing On light response (Morgans et al. 2010). The other two, the horizontal cells and Off bipolar cells are sign conserving but use pharmacologically discrete ionotropic glutamate receptors. Thus three cell types perform different functions that are enabled by their specific and distinct glutamate receptors (Miller & Slaughter, 1986). The photoreceptor synapse is playing the game of telephone, sending out one message that is heard differently by each cell type. In the mouse retina, where at least 10 types of cone bipolar cells have been identified (Wassle et al. 2009; Helmstaedter et al. 2013), each of the majority middle wavelength sensitive cones contacts all of the bipolar cell types with only one exception (Haverkamp et al. 2005). But the diversity of postsynaptic receptors clearly means this divergence is not redundant. Bipolar cells, the interlocutors between the cone light sensors and the ganglion cell spike encoders, first establish parallel visual pathways. The DeVries lab has redefined this synapse. In a ground-breaking study, he found that the Off bipolar cells can be further subdivided and that each subtype expresses a different ionotropic receptor (DeVries, 2000). There are AMPA-expressing Off bipolar cells (termed cb2) that press their receptors very close to the cone release sites while other, kainate-expressing Off bipolar cells (termed cb1/cb3), are positioned at the base of the synaptic terminal far from release sites and consequently sense lower and more prolonged levels of glutamate (DeVries et al. 2006). But there are differences in the glutamate responses of the kainate receptor-expressing neurons that the current paper disentangles. The cb1 synapses are relatively simple, dominated by GluK1 receptors. The cb3 synapses appear more complex, probably GluK1/GluK5-containing heteromers and perhaps also containing GluK3. The receptors may also be modulated by Neto1. Furthermore, about 20% of the cb3 current derives from AMPA receptors. There may be further layers of complexity at the Off bipolar synapse. The cb1 kainate receptors have two distinct rates of recovery from desensitization, indicating either two desensitized states of the protein or modulation of the receptor to alter it recovery rate. In mouse retina the AMPA (type 1), kainate (type 2/3a), and mixed AMPA–kainate receptor (type 3b/4) Off bipolar cell types can also be distinguished, but do not match the homologous bipolar cells in guinea-pig (Puller et al. 2013). Either the homology classification needs revision or there is an intriguing flexibility in receptor expression. Furthermore, AMPA and kainate receptors in the mixed mouse bipolar cell do not co-localize, suggesting they can be differentially activated. Each new level of receptor complexity has revealed additional coding mechanisms and this is only the first retinal synapse.

Dichromatic colour vision in wallabies as characterised by three behavioural paradigms.

Despite lacking genetic evidence of a third cone opsin in the retina of any Australian marsupial, most species tested so far appear to be trichromatic. In the light of this, we have re-examined colour vision of the tammar wallaby which had previously been identified as a dichromat. Three different psychophysical tests, based on an operant conditioning paradigm, were used to confirm that colour perception in the wallaby can be predicted and conclusively explained by the existence of only two cone types. Firstly, colour-mixing experiments revealed a Confusion Point between the three primary colours of a LCD monitor that can be predicted by the cone excitation ratio of the short- and middle-wavelength sensitive cones. Secondly, the wavelength discrimination ability in the wallaby, when tested with monochromatic stimuli, was found to be limited to a narrow range between 440 nm and 500 nm. Lastly, an experiment designed to test the wallaby’s ability to discriminate monochromatic lights from a white light provided clear evidence for a Neutral Point around 485 nm where discrimination consistently failed. Relative colour discrimination seemed clearly preferred but it was possible to train a wallaby to perform absolute colour discriminations. The results confirm the tammar wallaby as a dichromat, and so far the only behaviourally confirmed dichromat among the Australian marsupials.

New Genetic Technology May Help Pilots, Aviation Employees, and Color Vision Researchers

Color vision research is not new for the Federal Aviation Administration (FAA); the Civil Aerospace Medical Institute has been conducting color vision research and publishing the results since 1967 ( 3 ). The FAA originally initiated color vision research because of the emerging use of color coding in the airport environment and the FAA has continued a line of color vision research because of the increasing use of color coding resulting from changing technology inside the cockpit, on air traffic control displays, and in the airport environment. Color can be used to convey meaning without supplemental signage such as the ubiquitous traffic signal that alerts drivers to proceed with caution via a yellow flashing light or to stop via a red flashing light. However, that meaning is only conveyed if the driver can distinguish between the yellow and the red colors. Approximately 8 to 10% of the male population ( 5 ) has a congenital color vision deficiency and, depending upon the type and severity of that deficiency, that task of interpreting the meaning of color coding may be difficult or impossible. Consequently, the FAA has long maintained a color vision standard for aero-medical screening to ensure that pilots and air traffic controllers can perform safety-related tasks without adverse consequences. Throughout the past few years, the FAA has explored a variety of color vision tests, searching for a valid screening test that has high sensitivity and specificity, meaning the ability to detect the presence or absence of the deficiency, respectively. Basically, color vision tests can be categorized as diagnostic, screening, or occupational tests. Diagnostic tests are designed to specifically diagnose the type and degree of deficiency, the screening tests focus on differentiating between normal or deficient color vision, and the occupational tests seek to separate those capable versus incapable of certain tasks such as identifying colors of wires or lights (e.g., the Farnsworth Lantern test that was developed to assess the ability of potential Navy signalmen for identifying red, green, and white lights). A few tests have been developed for the purpose of precisely diagnosing and classifying color vision; however, when color vision test scores are compared to performance on occupational tasks such as identifying or discriminating colors used in signal lights, precision approach path indicator (PAPI) lights, colored navigation lights, color coded map reading tasks, color coded air traffic control displays, and cockpit displays, a specific cut-point on those selection tests has not been found that can fully separate those who can from those who cannot accurately perform the color-coded pilot or air traffic control tasks. Some tests, including new computerized instruments, have been designed to differentiate defects involving the long wavelength sensitive cones (protan-type), middle wavelength sensitive cones (deutan-type), and short wavelength sensitive cones (tritan-type). Congenital protan and deutan deficiencies are, collectively, extremely common, affecting 1 in 12 men and 1 in 230 women; however, recent evidence indicates that tritan defects are virtually never present at birth (e.g., congenital) and the inherited forms involve S cone photoreceptor degeneration that develops later in life with the exact onset depending upon the specific mutation ( 1, 4 ). Thus, the exact frequency of inherited tritan defects is uncertain; however, it is probably less than 1 in 500. In part, because the underlying pathophysiology has not been well understood, few tests have been available that are capable of detecting tritan deficiencies. In the past, those tests included the single Farnsworth F2 pseudoisochromatic plate (PIP), the Moreland anomaloscope, the Hardy, Rand, Rittler PIP test, and, most recently, the Oculus anomaloscope. Consequently, the occupational color vision tests used by most agencies only screen for the most common (protan and deutan) types of defects. The newly developed computerized color vision tests, including the Colour Assessment and Diagnostic Test, the Cambridge Colour Test, the Cone Contrast Test, and the Computerized Color Vision Test, are all designed to detect tritan defects. However, tritan weaknesses have been noted in several of the FAA ‘ s recent studies in much higher than the traditionally expected numbers and diagnostic agreement is low among those tests when tritan deficiencies are involved. In the past, the FAA and other regulatory organizations have not, or have rarely, required tritan color vision screening in their occupational screening because of the following three factors: the rarity of the congenital defect, the unknown number of individuals affected by acquired deficiencies, and the lack of effective, reliable, valid, and affordable equipment with which to diagnose the deficiency.

Processing of S-cone signals in the inner plexiform layer of the mammalian retina

Color information is encoded by two parallel pathways in the mammalian retina. One pathway compares signals from long- and middle-wavelength sensitive cones and generates red-green opponency. The other compares signals from short- and middle-/long-wavelength sensitive cones and generates blue-green (yellow) opponency. Whereas both pathways operate in trichromatic primates (including humans), the fundamental, phylogenetically ancient color mechanism shared among most mammals is blue-green opponency. In this review, we summarize the current understanding of how signals from short-wavelength sensitive cones are processed in the primate and nonprimate mammalian retina, with a focus on the inner plexiform layer where bipolar, amacrine, and ganglion cell processes interact to facilitate the generation of blue-green opponency.

V1 mechanisms underlying chromatic contrast detection

To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of "cardinal color directions," for which V1 neurons are particularly sensitive. We conclude that at detection threshold--as shown previously with high-contrast stimuli-V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red-green and blue-yellow categories.

Estimated absorbance spectra of the visual pigments of the North Atlantic right whale (Eubalaena glacialis)

To assess the spectral sensitivities of the retinal visual pigments from the North Atlantic right whale (Eubalaena glacialis), we have cloned and sequenced two exons from the rod opsin gene and two exons from the middle-wavelength sensitive (MWS) cone opsin gene in order to determine the amino acids at positions known to be key regulators of the spectral location of the absorbance maximum (λmax). Based on previous mutagenesis models we estimate that the right whale possesses a rod visual pigment with a λmax of 499 nm and a MWS cone visual pigment with a λmax of 524 nm. Although the MWS cone visual pigment from the right whale is blue-shifted in its spectral sensitivity like those from odontocetes, the spectral sensitivity of the right whale rod visual pigment is similar to those from terrestrial mammals.

Combination of rod and cone inputs in parasol ganglion cells of the magnocellular pathway

This study investigates how rod and cone inputs are combined in the magnocellular (MC) pathway in the mesopic luminance range, when both rods and cones are active. Responses of parafoveal MC ganglion cells from macaque retina were measured as a function of temporal frequency (0.62-20 Hz) or contrast (0.05-0.55) at mesopic light levels (0.2, 2, 20, and 200 td). Stimuli were of three modulation types: (1) isolated rod stimuli (only rod signals were modulated), (2) isolated cone stimuli (only cone luminance signals from long- and middle-wavelength sensitive cones were modulated), and (3) combined rod and cone stimuli (both rod and cone luminance signals were modulated in phase, as with conventional stimuli). The results showed that under mesopic conditions, the relative rod and cone inputs to the MC cells varied with light level and they are combined linearly prior to saturation. Further, rod contrast gain is relatively stable over the mesopic range while cone contrast gain increased with light level. Finally, the measured rod and cone inputs are consistent with the measured human temporal contrast sensitivity functions under comparable stimulation conditions.

The effects of longitudinal chromatic aberration and a shift in the peak of the middle-wavelength sensitive cone fundamental on cone contrast

Longitudinal chromatic aberration is a well-known imperfection of visual optics, but the consequences in natural conditions, and for the evolution of receptor spectral sensitivities are less well understood. This paper examines how chromatic aberration affects image quality in the middle-wavelength sensitive (M-) cones, viewing broad-band spectra, over a range of spatial frequencies and focal planes. We also model the effects on M-cone contrast of moving the M-cone fundamental relative to the long- and middle-wavelength (L- and M-cone) fundamentals, while the eye is accommodated at different focal planes or at a focal plane that maximizes luminance contrast. When the focal plane shifts towards longer (650 nm) or shorter wavelengths (420 nm) the effects on M-cone contrast are large: longitudinal chromatic aberration causes total loss of M-cone contrast above 10–20 c/d. In comparison, the shift of the M-cone fundamental causes smaller effects on M-cone contrast. At 10 c/d a shift in the peak of the M-cone spectrum from 560 to 460 nm decreases M-cone contrast by 30%, while a 10 nm blue-shift causes only a minor loss of contrast. However, a noticeable loss of contrast may be seen if the eye is focused at focal planes other than that which maximizes luminance contrast. The presence of separate long- and middle-wavelength sensitive cones therefore has a small, but not insignificant cost to the retinal image via longitudinal chromatic aberration. This aberration may therefore be a factor limiting evolution of visual pigments and trichromatic color vision.

Distinguishing L from M photopigment coding sequences by hybridization to novel locked nucleic acid (LNA) oligonucleotide probes

Many attempts have been made over the years to distinguish human and primate L (long-wavelength sensitive) from M (middle-wavelength sensitive) cone photoreceptors using either immunohistochemistry or in situ hybridization. These attempts have been unsuccessful due to the very high degree of identity between the sequences of the L and M proteins and encoding mRNAs. The recent development of chemically modified oligonucleotide probes, referred to as locked nucleic acid (LNA) probes, has shown that they hybridize with much greater affinity and specificity to the target nucleic acid. This has greatly increased the potential for differentiating L from M cones by in situ hybridization. We have designed LNA oligonucleotide probes that are complementary to either the L or M coding sequences located in exon 5 of the Macaca nemestrina L and M pigment genes. We have shown that the LNA-M and LNA-L probes hybridize specifically to their respective target nucleic acid sequences in vitro. This result strongly suggests that these probes would be instrumental in rapidly distinguishing L from M cone in the entire retina, and in defining the cone mosaic during development and in adults.

Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram

The topographical distribution of relative sensitivity to red and green lights across the retina was assayed using a custom-made wide-field color multifocal electroretinogram apparatus. There were increases in the relative sensitivity to red compared to green light in the periphery that correlate with observed increases in the relative amount of long (L) compared to middle (M) wavelength sensitive opsin mRNA. These results provide electrophysiological evidence that there is a dramatic increase in the ratio of L to M cones in the far periphery of the human retina. The central to far peripheral homogeneity in cone proportions has implications for understanding the developmental mechanisms that determine the identity of a cone as L or M and for understanding the circuitry for color vision in the peripheral retina.

Amacrine cell contributions to red-green color opponency in central primate retina: A model study

To investigate the contributions of amacrine cells to red-green opponency, a linear computational model of the central macaque retina was developed based on a published cone mosaic. In the model, amacrine cells of ON and OFF types received input from all neighboring midget bipolar cells of the same polarity, but OFF amacrine cells had a bias toward bipolar cells whose center responses were mediated by middle wavelength sensitive cones. This bias might arise due to activity dependent plasticity because there are midget bipolar cells driven by short wavelength sensitive cones in the OFF pathway. The model midget ganglion cells received inputs from neighboring amacrine cells of both types. As in physiological experiments, the model ganglion cells showed spatially opponent responses to achromatic stimuli, but they responded to cone isolating stimuli as though center and surround were each driven by a single cone type. Without amacrine cell input, long and middle wavelength sensitive cones contributed to both the centers and surrounds of model ganglion cell receptive fields. According to the model, the summed amacrine cell input was red-green opponent even though inputs to individual amacrine cells were unselective. A key prediction is that GABA and glycine depolarize two of the four types of central midget ganglion cells; this may reflect lower levels of the potassium chloride co-transporter in their dendrites.

Spectral absorbance, structure, and population density of photoreceptors in the retina of the lake sturgeon (Acipenser fulvescens)

Lake sturgeon ( Acipenser fulvescens Rafinesque, 1817) photoreceptors were studied with scanning electron microscopy and microspectrophotometry. The retina contains both rods and cones, with cones estimated composing about 30% of the photoreceptor population. Only large single cones were identified and they are similar to those found in other species of the order Acipenseriformes. The rods are large, with long, broad outer segments, and are similar to the dominant rod found in other sturgeons and the North American paddlefish ( Polyodon spathula (Walbaum, 1792)). Mean (SD) rod packing density at 22 624 ± 3 509 rods/mm2 is low compared with those of other animals that function primarily in dim light. The visual pigment of the rods has a mean (SD) peak absorbance (λmax) at 541 ± 2 nm. Three different cone populations were identified: a long wavelength sensitive cone containing a visual pigment with λmax at 619 ± 3 nm; middle wavelength sensitive cone with λmax at 538 ± 1 nm; and short wavelength sensitive cone with λmax at 448 ± 1 nm. All the visual pigments are based on the vitamin A2 chromophore.

Topography of long- and middle-wavelength sensitive cone opsin gene expression in human and Old World monkey retina

The topographical distributions of the relative ratio of long- (L) and middle- (M) wavelength sensitive cone opsin messenger RNA (mRNA) in human and baboon retinas were mapped using real-time polymerase chain reaction. The L:M mRNA ratio increased in a central-to-peripheral gradient in both species, being quite pronounced for humans.

X-Linked Cone Dysfunction Syndrome with Myopia and Protanopia

To perform a detailed clinical, psychophysical, and molecular assessment of members of 4 families with an unusual X-linked cone dysfunction syndrome associated with myopia. Affected and unaffected members of 4 British nonconsanguineous families. Subjects underwent both detailed clinical examination and psychophysical testing. After informed consent was obtained, blood samples were taken for DNA extraction, and molecular genetic analysis was performed. The strategy for molecular analysis was to amplify the coding regions of the long and middle wavelength-sensitive cone opsin genes and the upstream locus control region by polymerase chain reaction and to examine these fragments for mutations by sequencing of DNA. The phenotype was almost identical in all 4 families, consisting of moderate to high myopia, astigmatism, moderately reduced acuity, and normal fundi. Electroretinography showed abnormal cone but normal rod responses. Psychophysical testing showed a selective impairment of long cones in combination with well-preserved middle cone and short cone function. There was no evidence to suggest that the phenotype was progressive. Molecular analysis of the X-linked opsin gene array in the 4 families indicated that affected males have inherited the same X-chromosome from their mother. In 2 families, a long/middle hybrid gene was detected. In a third family, the commonly described deleterious Cys203Arg amino acid substitution was identified in both the long and middle opsin genes. In the fourth family, the only abnormality was absence of a middle opsin exon 2; the cause of the protanopia in this family is uncertain. The X-linked cone dysfunction syndrome associated with myopia and dichromacy described here has many similarities to Bornholm eye disease, a condition previously mapped to Xq28. Except for the Cys203Arg substitution in one family, no alterations in the opsin gene array were identified that could underlie the cone dysfunction. It is therefore possible that the cone dysfunction may have a genetic origin different from that of the dichromacy.