Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rod Opsins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1990

Functional expression in vitro of bovine visual rhodopsin.

Expression of functionally active bovine visual rhodopsin was achieved by sequential transcription and translation in vitro of rhodopsin gene cDNA with co-translational insertion of the protein into phosphatidylcholine liposomes. The recombinant rhodopsin has functional, spectral and immunochemical properties similar to those of natural rhodopsin from bovine retina. Two mutant rhodopsins, Cys316----Ser and Asp330----Asn, Asp331----Asn, were produced by oligonucleotide-directed mutagenesis. The first mutation does not affect rhodopsin's ability to stimulate transducin GTPase and visual cGMP phosphodiesterase activities, while the second double mutation leads to a sharp decrease in rhodopsin activity.

Animals↗
PubMed1993

Design of a discriminating fingerprint for G-protein-coupled receptors.

A systematic method for designing discriminating protein sequence fingerprints is described. The approach used is iterative, and diagnostic performance is evaluated in terms of the relative abilities of sequences to match with individual elements of the fingerprint. The method allows complete protein folds to be characterized in terms of a number of separate 'features', without the requirement to define specific intervals between them, and is described here with reference to the derivation of a fingerprint for G-protein-coupled receptors: this comprises the seven hydrophobic regions shown by protein chemistry approaches to be membrane-spanning. The fingerprint is potently diagnostic of all sequences of this type in the database in which it was derived (the OWL composite sequence database, version 8.1), and has continued to perform well on subsequent database updates, identifying 240 receptors in OWL17.0. Results are compared with a commonly used pattern template for this class of receptors. The investigation suggests that discriminating power is improved in the fingerprint approach because the recognition of individual features is made mutually conditional. Furthermore, by avoiding the definition of predetermined feature separations, members of protein families possessing all or only part of the fingerprint may be identified.

Algorithms↗
PubMed1994

Sequence divergence analysis for the prediction of seven-helix membrane protein structures: II. A 3-D model of human rhodopsin.

A three-dimensional (3-D) model of the transmembrane domain of human rhodopsin was predicted from the sequence divergence analysis of 42 sequences of rhodopsins and visual pigments without a template. The prediction steps include multiple sequence alignment, calculation of a variability profile of the aligned sequences, use of the variability profile to identify the boundaries of transmembrane regions, their secondary structure and packing shape in a helix bundle, prediction of side-chain conformations and structure refinement. The identification of the retinal binding site was assisted by its known covalent linkage with K296. The structural features of the predicted 3-D model are in good agreement with a low resolution electron density map of bovine rhodopsin and with residues in contact with retinal as determined experimentally.

Amino Acid Sequence↗
PubMed1996

Cytophilic immunoglobulins revisited via natural killer cells.

Cytophilia is one of the biologic properties of the Fc region of immunoglobulins operationally defined as the ability of an antibody molecule to attach to certain cell types before combination with antigen. By attachment of cytophilic antibody to membrane Fc receptors, cells become "armed" with antibodies and able to interact specifically with soluble or particulate antigens. In contrast to this cytophilia, the so-called opsonic antibody binds to FcR of various cell types only after it has complexed with antigen. In spite of knowledge of cytophilic properties of immunoglobulins for more than 30 years and an impressive accumulation of facts regarding the structure and function of cell-surface FcR binding IgG, IgE, or IgA molecules, less progress has been made in understanding the molecular basis of cytophilia. Our extensive studies of the structural and functional aspects of the interaction of IgG in monomeric form with human natural killer cells, via the type IIIA IgG Fc receptor (Fc gamma RIIIA), provide a focal point for revisiting this major pathway of direct and continuous communication between the humoral and cellular compartments of the immune system.

Animals↗
PubMed2004

Melanopsin containing retinal ganglion cells are light responsive from birth.

Photoentrainment of the biological clock located in the suprachiasmatic nucleus (SCN) begins shortly after birth. Here we show using c-FOS immunoreactivity as a marker for neuronal activity that the melanopsin/PACAP containing retinal ganglion cells (RGCs) which project to the SCN as the retinohypothalamic tract (RHT) are responsive to light from birth. After postnatal day 12 where the classical photoreceptors become functional other RGCs and cells of the inner nuclear cell layer also respond to light. Light also induces c-FOS immunoreactivity in the retinorecipient SCN from the first postnatal day and accordingly PACAP immunoreactive fibres are visible in the SCN. The results indicate that the retina is light responsive before functional rods and cones and that the RHT is functional from birth supporting that photoentrainment of the biological clock begins shortly after birth.

Age Factors↗
PubMed2001

Age-related changes in the mouse outer retina.

PURPOSE: To define the physiological and structural changes that may accompany aging in the normal mouse retina. METHODS: C57BL/6 mice were maintained under cyclic light for either 2, 6, or 12 months. After rod- and cone-mediated corneal electroretinograms (ERG's) were recorded from anesthetized animals, the retinal structure was quantitatively examined. Photoreceptor cell density was measured within 100-microm regions of the central superior and inferior retina. Cone photoreceptor subtypes were identified by immunocytochemistry. RESULTS: The amplitudes of rod- and cone-mediated ERG's were reduced in older mice, although the overall ERG wave-form did not change appreciably and implicit times were not changed in an age-dependent fashion. In comparison, there was no significant age-related decline in rod or cone photoreceptor density. CONCLUSIONS: The amplitude of the mouse ERG declines with age. This change does not appear to reflect a change in the structural integrity of the photoreceptor cells. In functional studies of murine models of late-onset retinal disorders, it will be important to take these changes into consideration.

Aging↗
PubMed2004

Ocular fundus images by scanning laser ophthalmoscopy in a patient with enhanced S-cone syndrome.

PURPOSE: To present ocular fundus images in a patient with enhanced S-cone syndrome by scanning laser ophthalmoscopy. A 34-year-old Japanese woman whose parents were consanguineous showed mismatched electroretinographic responses to photopically balanced single-flash stimuli, with a larger signal to blue light than to red light. The central macula lacked a foveal reflex, and the surface was dull. Yellowish flecks and retinal pigment epithelium atrophy were evident in a ring at and around the vascular arcades. Faint black pigmentation was deposited in the mid peripheral retina. METHODS: The ocular fundus of the patient was observed by scanning laser ophthalmoscopy with the use of an argon blue laser (wavelength, 488 nm), a helium-neon laser (633 nm), and an infrared laser (780 nm). RESULTS: The argon blue laser showed numerous black spots of pigment, which were observed as faint pigmentation by conventional ophthalmoscopy. The spots were more enhanced with the argon blue laser than with the helium-neon laser. The white spots, which corresponded to the yellowish flecks in a ring at and around the vascular arcades, were more enhanced with the helium-neon laser than with the argon blue or infrared laser. Hypopigmentation of the retinal pigment epithelium was best shown with the infrared laser. CONCLUSION: An abnormality of the retinal structure in enhanced S-cone syndrome may exist in the inner and outer retinal levels, in at least some patients.

Adult↗
PubMed2006

Influence of clinical factors on blue-on-yellow perimetry for diabetic patients without retinopathy: comparison with white-on-white perimetry.

PURPOSE: To investigate the influence of clinical factors (duration of diabetes mellitus, fasting blood sugar level, fructosamine concentration, and hemoglobin A1c) on blue-on-yellow (B-on-Y) perimetry compared with white-on-white (W-on-W) perimetry for diabetics without retinopathy. METHODS: Both B-on-Y perimetry and W-on-W perimetry were performed for 33 diabetics without retinopathy. Thirty-three subjects with healthy eyes served as age-matched controls. RESULTS: For both diabetic patients and controls, mean deviation (MD) and corrected pattern SD of perimetry showed no difference irrespective of B-on-Y or W-on-W perimetry. For diabetics, MD of B-on-Y perimetry decreased in proportion to the morbid period with diabetes mellitus, with the same being true with deterioration of the clinical factors. Multiple regression analysis disclosed no differences in MD of clinical factors for W-on-W perimetry, despite the duration of diabetes mellitus exerting a significant influence on MD of B-on-Y perimetry. CONCLUSION: Even at the premorbid stage of diabetic retinopathy, longer duration of diabetes mellitus and longer persistence of poorly controlled diabetes mellitus are associated with an insidious progress of dysfunction in the retinal blue cone system.

Adult↗
PubMed1992

Sequence divergence and copy number of the middle- and long-wave photopigment genes in Old World monkeys.

We have studied the sequence and organization of the genes for the middle-wave (MW) and long-wave (LW) cone photopigment genes in six species of Old World monkeys. Previous studies have shown that the MW and LW pigments of all six species exhibit peak sensitivities near 535 nm and 565 nm, respectively, and thus resemble the equivalent human pigments. In the case of man, the protein components of the MW and LW photopigments differ by 15 amino acids, although only seven of these differences involve non-homologous substitutions and are therefore candidates for a role in spectral tuning. Regions corresponding to exons 4 and 5 of these genes, and including five such candidate sites, were sequenced in the Old World monkeys. In contrast to the equivalent human genes, substitutions were found at two of these sites, position 233 and 309 of the MW gene in all six species. The role of amino acid substitutions in the spectral tuning of these photopigments is discussed. A comparison of the nucleotide sequences of the MW and LW genes provides evidence for sequence homogenization within species; the role of gene conversion in the evolution of these genes is discussed. The close juxtaposition and homology of the MW and LW genes on the X chromosome is thought to underlie the high frequency of colour vision defects in man and the presence in many individuals of extra copies of the MW gene. A study of a group of talapoin (Ceropithecus talapoin) monkeys has revealed a similar numerical polymorphism for this gene to that present in man. In contrast to the situation in man, where the MW and LW genes may contain a shortened first intron, restriction digests of genomic DNA showed that the size of this intron does not differ across the six species of Old World monkeys examined.

Amino Acid Sequence↗
PubMed2000

Demonstration of a foraging advantage for trichromatic marmosets (Callithrix geoffroyi) dependent on food colour.

It has been suggested that the major advantage of trichromatic over dichromatic colour vision in primates is enhanced detection of red/yellow food items such as fruit against the dappled foliage of the forest. This hypothesis was tested by comparing the foraging ability of dichromatic and trichromatic Geoffroy's marmosets (Callithrix geoffroyi) for orange- and green-coloured cereal balls (Kix) in a naturalized captive setting. Trichromatic marmosets found a significantly greater number of orange, but not green, Kix than dichromatic marmosets when the food items were scattered on the floor of the cage (at a potential detection distance of up to 6 m from the animals). Under these conditions, trichromats but not dichromats found significantly more orange than green Kix, an effect that was also evident when separately examining the data from the end of the trials, when the least conspicuous Kix were left. In contrast, no significant differences among trichromats and dichromats were seen when the Kix were placed in trays among green wood shavings (detection distance < 0.5 m). These results support an advantage for trichromats in detecting orange-coloured food items against foliage, and also suggest that this advantage may be less important at shorter distances. If such a foraging advantage for trichromats is present in the wild it might be sufficient to maintain the colour vision polymorphism seen in the majority of New World monkeys.

Alleles↗
PubMed1993

Acidic fibroblast growth factor is expressed abundantly by photoreceptors within the developing and mature rat retina.

In order to further understand the role(s) of fibroblast growth factors (FGFs) in the development, differentiation and function of the central nervous system, we analysed the expression of the mRNA, and the presence and tissue distribution of the translated product, of one member of the FGF family, acidic FGF (aFGF), within the mammalian retina. Firstly, the relative abundance of aFGF mRNA was assayed in embryonic (between 14 and 17 days of gestation), postnatal (between 1 and 17 days after birth) and adult rat retina by quantitative reverse transcription-coupled polymerase chain reaction amplification using specific aFGF oligonucleotides. The level of expression remained uniformly low throughout the embryonic period and until postnatal day 7. Therefore the quantity of aFGF mRNA increased rapidly, reaching 80% of adult levels by eye opening (postnatal day 13). Adult levels were three-fold higher than at early developmental times. In situ hybridization of adult rat retina using specific antisense aFGF riboprobes revealed labelling in all cellular layers. Antisera raised against recombinant human aFGF revealed very little labelling of 4-day postnatal retina, but by postnatal days 8 and 17 immunoreactive aFGF was localized mainly within the photoreceptor cell bodies. Western blots of retinal extracts derived from 17-day embryonic, 4-day postnatal and adult retina probed with the same antibody revealed a single immunoreactive band of the expected molecular weight (18 kDa) in all extracts. Thus aFGF is mostly transcribed and translated within the retina subsequent to the major steps of cell birth, migration and differentiation, and seems to be abundantly expressed by maturing photoreceptor cells.

Animals↗
PubMed2003

Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice.

Non-rod, non-cone ocular photoreceptors have been shown to mediate a range of irradiance detection tasks. The strongest candidates for these receptors are melanopsin-positive retinal ganglion cells (RGCs). To provide a more complete understanding of these receptors in vivo, we have utilized a mouse that lacks rod and cone photoreceptors (rd/rd cl) and compared these animals to congenic wild-types. Using real-time polymerase chain reaction and immunohistochemistry, we address the following. (1) Is Fos expression within these RGCs driven by an input from the rods/cones or is it the product of the intrinsic photosensitivity of these neurons? We demonstrate that most Fos expression across the entire retina is due to the rods/cones, but in the absence of these photoreceptors, light will induce Fos within melanopsin RGCs. (2) Could the reported age-related decline in circadian photosensitivity of rodents be linked to changes in the population of melanopsin RGCs? We show that old mice experience an approximately 40% reduction in melanopsin RGCs. (3) Does the loss of inner retinal neurons affect the responses of melanopsin RGCs? Aged (approximately 700 days) rd/rd cl mice lose most of their inner retina but retain the retinal ganglion cell layer. In these mice, the proportion of melanopsin RGCs that express Fos in response to light is significantly reduced. Collectively, our data suggest that melanopsin RGCs form a heterogeneous population of neurons, and that most of the light-induced c-fos expression within these cells is associated with the endogenous photosensitivity of these neurons.

Aging↗
PubMed2005

Dopamine regulates melanopsin mRNA expression in intrinsically photosensitive retinal ganglion cells.

In mammals a subpopulation of retinal ganglion cells are intrinsically photosensitive (ipRGCs), express the photopigment melanopsin, and play an important role in the regulation of the nonimage-forming visual system. We have recently reported that melanopsin mRNA and protein levels in the rat retina are under photic and circadian control. The aim of the present work was to investigate the mechanisms that control melanopsin expression in the rat retina. We discovered that dopamine (DA) is involved in the regulation of melanopsin mRNA, possibly via dopamine D2 receptors that are located on these ipRGCs. Interestingly, we also discovered that pituitary adenylate cyclase-activating peptide (PACAP) mRNA levels are affected by DA. Dopamine synthesis and release in the retina are regulated by the rod and the cone photoreceptors via retinal circuitry; our new data indicate that DA controls melanopsin expression, indicating that classical photoreceptors may modulate the transcription of this new photopigment. Our study also suggests that DA may have an important role in mediating the light signals that are used for circadian entrainment and for other responses that are mediated by the nonimage-forming visual system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2006

The light-activated signaling pathway in SCN-projecting rat retinal ganglion cells.

In mammals, the master circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus. The period and phase of the circadian pacemaker are calibrated by direct photic input from retinal ganglion cells (RGCs). SCN-projecting RGCs respond to light in the absence of rod- and cone-driven synaptic input, a property for which they are termed intrinsically photosensitive. In SCN-projecting RGCs, light activates a nonselective cationic current that displays inward and outward rectification. The goal of the present study was to investigate the identity of the light-activated ion channel and the intracellular signaling pathway leading to its activation. We considered two candidate channels, cyclic nucleotide-gated (CNG) channels and transient receptor potential (TRP) channels, which mediate vertebrate and invertebrate phototransduction, respectively. We report that the intrinsic light response relies upon a G-protein-dependent process. Although our data indicate that cyclic nucleotides modulate the signaling pathway, CNG channels do not appear to conduct the light-activated current because (i) cyclic nucleotides in the pipette solution do not activate a conductance or completely block the light response, (ii) CNG channel blockers fail to inhibit the light response, (iii) the effects of internal and external divalent cations are inconsistent with their effects on CNG channels, and (iv) immunohistochemistry reveals no CNG channels in SCN-projecting RGCs. Finally, we show that the pharmacology of the light-activated channel resembles that of some TRPC channel family members; the response is blocked by lanthanides and ruthenium red and SK&F 96365, and is enhanced by flufenamic acid and 1-oleoyl-2-acetyl-sn-glycerol. Furthermore, immunohistochemical experiments reveal that TRPC6 is expressed in many RGCs, including those that express melanopsin.

Animals↗
PubMed2006

Synaptic inputs to retinal ganglion cells that set the circadian clock.

Melanopsin-containing retinal ganglion cells (RGCs) project to the suprachiasmatic nuclei (SCN) and mediate photoentrainment of the circadian system. Melanopsin is a novel retinal-based photopigment that renders these cells intrinsically photosensitive (ip). Although genetic ablation of melanopsin abolishes the intrinsic light response, it has a surprisingly minor effect on circadian photoentrainment. This and other non-visual responses to light are lost only when the melanopsin deficiency is coupled with mutations that disable classical rod and cone photoreceptors, suggesting that melanopsin-containing RGCs also receive rod- and cone-driven synaptic inputs. Using whole-cell patch-clamp recording, we demonstrate that light triggers synaptic currents in ipRGCs via activation of ionotropic glutamate and gamma-aminobutyric acid (GABA) receptors. Miniature postsynaptic currents (mPSCs) were clearly observed in ipRGCs, although they were less robust and were seen less frequently than those seen in non-ip cells. Pharmacological treatments revealed that the majority of ipRGCs receive excitatory glutamatergic inputs that were blocked by DNQX and/or kynurenic acid, as well as inhibitory GABAergic inputs that were blocked by bicuculline. Other ipRGCs received either glutamatergic or GABAergic inputs nearly exclusively. Although strychnine (Strych)-sensitive mPSCs were evident on many non-ipRGCs, indicating the presence of glycinergic inputs, we saw no evidence of Strych-sensitive events in ipRGCs. Based on these results, it is clear that SCN-projecting RGCs can respond to light both via an intrinsic melanopsin-based signaling cascade and via a synaptic pathway driven by classical rod and/or cone photoreceptors. It remains to be determined how the ipRGCs integrate these temporally distinct inputs to generate the signals that mediate circadian photoentrainment and other non-visual responses to light.

Animals↗
PubMed2001

An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans.

1. Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production. The retinal photopigment(s) transducing these light responses in humans have not been characterised. 2. Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum. Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16-18) of different wavelengths (lambda(max) 424, 456, 472, 496, 520 and 548 nm) and irradiances (0.7-65.0 microW cm(-2)). 3. At each wavelength, suppression of plasma melatonin increased with increasing irradiance. Irradiance-response curves (IRCs) were fitted and the generated half-maximal responses (IR(50)) were corrected for lens filtering and used to construct an action spectrum. 4. The resulting action spectrum showed unique short-wavelength sensitivity very different from the classical scotopic and photopic visual systems. The lack of fit (r(2) < 0.1) of our action spectrum with the published rod and cone absorption spectra precluded these photoreceptors from having a major role. Cryptochromes 1 and 2 also had a poor fit to the data. Fitting a series of Dartnall nomograms generated for rhodopsin-based photopigments over the lambda(max) range 420-480 nm showed that rhodopsin templates between lambda(max) 457 and 462 nm fitted the data well (r(2) > or =0.73). Of these, the best fit was to the rhodopsin template with lambda(max) 459 nm (r(2) = 0.74). 5. Our data strongly support a primary role for a novel short-wavelength photopigment in light-induced melatonin suppression and provide the first direct evidence of a non-rod, non-cone photoreceptive system in humans.

Adult↗
PubMed1997

Phototransduction cascade and circadian oscillator in chicken pineal gland.

The chicken pineal gland has an endogenous circadian oscillator that controls the diurnal oscillation of N-acetyltransferase activity responsible for melatonin rhythm. It has been speculated that the chicken pineal cell contains a photoreceptive molecule that receives the environmental light signal and transmits the signal to the oscillator for resetting the phase. In spite of several lines of evidence suggesting the similarity between retinal and pineal photon-signal transducing proteins, the identity of the photoreceptive molecule had been an open question. In 1994, we isolated a pineal cDNA encoding a novel photoreceptive molecule and named it "pinopsin." The protein expressed in 293EBNA cells bound 11-cis-retinal to form a blue-sensitive pigment with an absorption maximum at about 470 nm. A putative G-protein interaction site of pinopsin shared a relatively high similarity in amino acid sequence to that of rhodopsin, implying that pinopsin functionally couples with transducin or transducin-like G-protein(s) in the pineal cells. We have cloned a cDNA for chicken pineal transducin alpha-subunit, and the deduced amino acid sequence contained a potential site to be ADP-ribosylated by pertussis toxin (PTX). Therefore, the transducin-mediated pathway could be blocked by PTX, though previous studies showed that treatment of the cultured chicken pineal cells with PTX had no effect on the light-induced phase-shift of the oscillator. Accordingly, it is unlikely that transducin mediates the light-input pathway to the oscillator, which may involve PTX-insensitive G-protein(s) or some unidentified component(s). The G-protein coupled receptor-mediated signaling processes regulating melatonin synthesis are discussed.

Adenosine Diphosphate Ribose↗