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Results for “Retinal Rod Photoreceptor Cells”

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At least 919 records · Page 51Linked to original sources
PubMed1993

Full-field electroretinogram in a patient with cutaneous melanoma-associated retinopathy.

A patient operated for malignant melanoma developed night blindness and a sensation of shimmering light, strong enough to make him unable to work. Shortly afterwards, melanoma metastases became apparent. A full-field ERG examination showed absence of rod responses but normal cone amplitudes, suggesting a malfunctioning rod system in the retina. The patient was not on chemotherapy. A few similar cases have previously been reported. The disease appears to differ from the cancer-associated retinopathy (CAR) syndrome, which affects mainly the photoreceptor cells.

Electroretinography↗
PubMed2006

The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties.

The glutamic acid-rich protein-2 (GARP2) is a splice variant of the beta-subunit of the cGMP-gated ion channel of rod photoreceptors. GARP2 is believed to interact with several membrane-associated phototransduction proteins in rod photoreceptors. In this study, we demonstrated that GARP2 is a high affinity PDE6-binding protein and that PDE6 co-purifies with GARP2 during several stages of chromatographic purification. We found that hydrophobic interaction chromatography succeeds in quantitatively separating GARP2 from the PDE6 holoenzyme. Furthermore, the 17-kDa prenyl-binding protein, abundant in retinal cells, selectively released PDE6 (but not GARP2) from rod outer segment membranes, demonstrating the specificity of the interaction between GARP2 and PDE6. Purified GARP2 was able to suppress 80% of the basal activity of the nonactivated, membrane-bound PDE6 holoenzyme at concentrations equivalent to its endogenous concentration in rod outer segment membranes. However, GARP2 was unable to reverse the transducin activation of PDE6 (in contrast to a previous study) nor did it significantly alter catalysis of the fully activated PDE6 catalytic dimer. The high binding affinity of GARP2 for PDE6 and its ability to regulate PDE6 activity in its dark-adapted state suggest a novel role for GARP2 as a regulator of spontaneous activation of rod PDE6, thereby serving to lower rod photoreceptor "dark noise" and allowing these sensory cells to operate at the single photon detection limit.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Cell death precedes rod neurogenesis in embryonic teleost retinal development.

We measured cell death in the retinas of embryonic and adult teleost fish using TUNEL staining. Following a wave of cell birth during embryogenesis that generates all retinal cell types except rods, cell death occurs in all three nuclear layers. The lack of a corresponding pattern of cell death in the growing adult margin suggests different roles for death during embryogenesis and adult neurogenesis.

Animals↗
PubMed2002

Visualization of rod photoreceptor development using GFP-transgenic zebrafish.

Zebrafish retina contains five morphologically distinct classes of photoreceptors, each expressing a distinct type of opsin gene. Molecular mechanisms underlying specification of opsin expression and differentiation among the cell types are largely unknown. This is partly because mutants affected with expression of a particular class of opsin gene are difficult to find. In this study we established the transgenic lines of zebrafish carrying green fluorescent protein (GFP) gene under the 1.1-kb and 3.7-kb upstream regions of the rod-opsin gene. In transgenic fish, GFP expression initiated and proceeded in the same spatiotemporal pattern with rod-opsin gene. The retinal section from adult transgenic fish showed GFP expression throughout the rod cell layer. These results indicate that the proximal 1.1-kb region is sufficient to drive gene expression in all rod photoreceptor cells. These transgenic fish should facilitate screening of mutants affected specifically with rod-opsin expression or rod cell development by visualization of rod cells by GFP.

5' Untranslated Regions↗
PubMed1999

Time-resolved rhodopsin activation currents in a unicellular expression system.

The early receptor current (ERC) is the charge redistribution occurring in plasma membrane rhodopsin during light activation of photoreceptors. Both the molecular mechanism of the ERC and its relationship to rhodopsin conformational activation are unknown. To investigate whether the ERC could be a time-resolved assay of rhodopsin structure-function relationships, the distinct sensitivity of modern electrophysiological tools was employed to test for flash-activated ERC signals in cells stably expressing normal human rod opsin after regeneration with 11-cis-retinal. ERCs are similar in waveform and kinetics to those found in photoreceptors. The action spectrum of the major R(2) charge motion is consistent with a rhodopsin photopigment. The R(1) phase is not kinetically resolvable and the R(2) phase, which overlaps metarhodopsin-II formation, has a rapid risetime and complex multiexponential decay. These experiments demonstrate, for the first time, kinetically resolved electrical state transitions during activation of expressed visual pigment in a unicellular environment (single or fused giant cells) containing only 6 x 10(6)-8 x 10(7) molecules of rhodopsin. This method improves measurement sensitivity 7 to 8 orders of magnitude compared to other time-resolved techniques applied to rhodopsin to study the role particular amino acids play in conformational activation and the forces that govern those transitions.

Cell Fusion↗
PubMed2005

Expression and localization of an exogenous G protein-coupled receptor fused with the rhodopsin C-terminal sequence in the retinal rod cells of knockin mice.

Vertebrate rod cell outer segments are highly differentiated compartments consisting of closely packed disk membranes, in which the photoreceptor rhodopsin is embedded at high density. To explore the unusually efficient mechanism of rhodopsin biosynthesis, folding and transport, we challenged it with the ectopic expression in rod cells of human endothelin receptor subtype B (hET(B)R) fused with the C-terminal 10 residues of rhodopsin, under the control of the mouse opsin promoter/enhancer, by gene targeted replacement (knockin), because the C-terminal eight residues are essential to target rhodopsin to the outer segment. The hET(B)R, a type-I G protein-coupled receptor, was successfully expressed and folded in a functional structure in the rod cells of knockin mice. However, while the mRNA level of hET(B)R was one tenth of that of rhodopsin, the hET(B)R protein level was approximately one-thousandth of the rhodopsin level in heterozygous mice, suggesting an intrinsically distinct efficiency in the production of functional receptor protein. In addition, a substantial fraction of the hET(B)R was successfully transported to the outer segment, suggesting that the addition of the C-terminal sequence of rhodopsin enabled hET(B)R to be translocated to the outer segment.

Animals↗
PubMed1996

Characterization and chromosomal localization of the gene for human rhodopsin kinase.

G-protein-dependent receptor kinases (GRKs) play a key role in the adaptation of receptors to persistent stimuli. In rod photoreceptors rhodopsin kinase (RK) mediates rapid desensitization of rod photoreceptors to light by catalyzing phosphorylation of the visual pigment rhodopsin. To study the structure and mechanism of GRKs in human photoreceptors, we have isolated and characterized cDNA and genomic clones derived from the human RK locus using a bovine rhodopsin kinase cDNA fragment as a probe. The RK locus, assigned to chromosome 13 band q34, is composed of seven exons that encode a protein 92% identical in amino acid sequence to bovine rhodopsin kinase. The marked difference between the structure of this gene and that of another recently cloned human GRK gene suggests the existence of a wide evolutionary gap between members of the GRK gene family.

Amino Acid Sequence↗
PubMed2002

Retinal processing: smaller babies thrown out with bathwater.

Rod bipolar cells in the mammalian retina receive synaptic input from many noisy rod photoreceptors. When photons are scarce, linear addition of inputs would swamp signals with noise. A nonlinearity at the synapse optimizes the signal to noise ratio.

Animals↗
PubMed2004

Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor alphavbeta5 for particle binding. Here, we tested RPE phagocytosis and retinal function in beta5 integrin--deficient mice, which specifically lack alphavbeta5 receptors. Retinal photoresponses severely declined with age in beta5-/- mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. beta5-/- RPE in culture failed to take up isolated photoreceptor particles. beta5-/- RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in beta5-/- retina. These results demonstrate an essential role for alphavbeta5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the beta5-/- integrin mouse strain as a new animal model of age-related retinal dysfunction.

Aging↗
PubMedDate not supplied

Multiple neuronal connexins in the mammalian retina.

Gap junctions are abundant in the mammalian retina and many neuronal types form neural networks. Several different neuronal connexins have now been identified in the mammalian retina. Cx36 supports coupling in the AII amacrine cell network and is essential for processing rod signals. Cx36 is probably also responsible for photoreceptor coupling. Horizontal cells appear to be extensively coupled by either Cx50 or Cx57. These results indicate that multiple neuronal connexins are expressed in the mammalian retina and that different cell types express different connexins.

Amacrine Cells↗
PubMed2001

Multiple inhibitory effects of zatebradine (UL-FS 49) on the electrophysiological properties of retinal rod photoreceptors.

Effects of the bradycardiac agent zatebradine (UL-FS 49) were determined in intracellular and patch-clamp experiments of amphibian rod photoreceptors. Zatebradine (0.3-100 microM) greatly enhanced the bright-light-induced hyperpolarization of membrane potential in frog retinal rods and caused damped oscillations during the membrane potential recovery phase. In inner segments of the rod photoreceptor cells, the hyperpolarization-activated inward current ( Ih) contributes to the recovery of the photoresponse. Patch-clamp recordings from newt rod photoreceptor cells revealed that zatebradine caused use- and concentration-dependent (0.1-100 microM) inhibition of Ih: conductance was reduced without effects on the reversal potential or activation voltage. Our data confirmed that the pharmacological properties of Ih in rod photoreceptors were similar to those of Ih in cardiac myocytes. In addition, zatebradine inhibited voltage-gated outward K+ currents ( IK), but did not affect L-type Ca2+ currents ( ICa). These results are consistent with the inhibition of IK and Ih by zatebradine in other cells, and may explain the oscillations evoked during the recovery phase of the membrane potential. These multiple actions of zatebradine on channels in rod photoreceptors may explain its effects on the electroretinogram (ERG) in vivo and its adverse effects on vision in clinical studies.

Animals↗
PubMed2001

[High resistance of the rat retina rods to hypoxia].

The amplitude of photoreceptor potential was shown to be constant in hypoxia. Under this condition, the energy support of the photoreceptor potential seems to be realized through an anaerobic process rather than the oxidative phosphorylation. The effect of hypoxia was shown to manifest itself in a decrease of the sagged peak part of the photoreceptor potential occurring in response to bright flashes. Such changes of wave form are typical for the case when the rod intracellular potential decreases. The decrease of response amplitude to bright flashes shortens the light scale of the amplitude/light intensity curve.

Animals↗
PubMed2005

Physiological properties of rod photoreceptor electrical coupling in the tiger salamander retina.

Using dual whole-cell voltage and current clamp recording techniques, we investigated the gap junctional conductance and the coupling coefficient between neighbouring rods in live salamander retinal slices. The application of sinusoidal stimuli over a wide range of temporal frequencies allowed us to characterize the band-pass filtering properties of the rod network. We found that the electrical coupling of all neighbouring rods exhibited reciprocal and symmetrical conductivities. On average, the junctional conductance between paired rods was 500 pS and the coupling coefficient (the ratio of voltage responses of the follower cell to those of the driver cell), or K-value, was 0.07. Our experimental results also demonstrated that the rod network behaved like a band-pass filter with a peak frequency of about 2-5 Hz. However, the gap junctions between adjacent rods exhibited linearity and voltage independency within the physiological range of rods. These gap junctions did not contribute to the filtering mechanisms of the rod network. Combined with the computational modelling, our data suggest that the filtering of higher frequency rod signals by the network is largely mediated by the passive resistive and capacitive (RC) properties of rod plasma membranes. Furthermore, we found several attributes of rod electrical coupling resembling the physiological properties of gene-encoded Cx35/36 gap junctions examined in other in vitro studies. This indicates that the previously found Cx35/36 expression in the salamander rod network may be functionally involved in rod-rod electrical coupling.

Action Potentials↗
PubMedDate not supplied

Activation of glutamate transporters in rods inhibits presynaptic calcium currents.

We found that L-glutamate (L-Glu) inhibits L-type Ca2+ currents (ICa) in rod photoreceptors. This inhibition was studied in isolated rods or rods in retinal slices from tiger salamander using perforated patch whole cell recordings and Cl(-)-imaging techniques. Application of L-Glu inhibited ICa by approximately 20% at 0.1 mM and approximately 35% at 1 mM. L-Glu also produced an inward current that reversed around ECl. The metabotropic glutamate receptor (mGluR) agonists t-ADA (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on ICa. However, the glutamate transport inhibitor, TBOA (0.1 mM), prevented L-Glu from inhibiting ICa. D-aspartate (D-Asp), a glutamate transporter substrate, also inhibited ICa with significantly more inhibition at 1 mM than 0.1 mM. Using Cl imaging, L-Glu (0.1-1 mM) and D-Asp (0.1-1 mM) were found to stimulate a Cl- efflux from terminals of isolated rods whereas the ionotropic glutamate receptor agonists NMDA, AMPA, and kainate and the mGluR agonist, 1S,3R-ACPD, did not. Glutamate-evoked Cl- effluxes were blocked by the glutamate transport inhibitors TBOA and DHKA. Cl- efflux inhibits Ca2+ channel activity in rod terminals (Thoreson et al. (2000), Visual Neuroscience 17, 197). Consistent with the possibility that glutamate-evoked Cl- efflux may play a role in the inhibition, reducing intraterminal Cl- prevented L-Glu from inhibiting ICa. In summary, the results indicate that activation of glutamate transporters inhibits ICa in rods possibly as a consequence of Cl- efflux. The neurotransmitter L-Glu released from rod terminals might thus provide a negative feedback signal to inhibit further L-Glu release.

Amino Acid Transport System X-AG↗
PubMed1994

[Function of the calcium-binding protein p26 (recoverin) in bovine retinal rods].

The bovine retina rod cell protein with an apparent M(r) 26 kDa (p26 [1] or recoverin [2]) was suggested to be a calcium-sensitive regulator of photoreceptor guanylate cyclase. The data obtained show that highly purified p26 is not capable of restoring guanylate cyclase in washed ROS membranes up to the level of a ROS suspension. At the same time we found that a Ca(2+)-sensitive complex of p26 and a protein with apparent M(r) 67 kDa, presumably rhodopsin kinase, is present in the ROS extract. We suggest that rhodopsin kinase can be a functional target for p26 in retina rod cells.

Animals↗
PubMed2004

Cytokine-induced activation of signal transducer and activator of transcription in photoreceptor precursors regulates rod differentiation in the developing mouse retina.

Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects during vertebrate retinogenesis, including regulation of photoreceptor cell differentiation. In the early postnatal mouse retina, CNTF induces rapid and transient phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3 and the extracellular signal-regulated kinase (ERK). Although both proliferating progenitor cells and postmitotic neurons respond directly to cytokine signals, CNTF elicits distinct phosphorylation patterns of STAT3 and ERK. CNTF stimulation induces low levels of STAT3 phosphorylation in progenitors and differentiated neurons but a robust STAT3 activation among postmitotic photoreceptor precursors expressing the cone-rod homeobox gene Crx and newly differentiated rod photoreceptors. In contrast, CNTF causes preferential phosphorylation of ERK in progenitor cells and photoreceptor precursors. Inhibition of the cytokine receptor gp130 using neutralizing antibodies reveals that gp130 is required for both CNTF-induced STAT3 and ERK phosphorylation. Perturbation of STAT signaling by a STAT inhibitor peptide or a dominant-negative STAT3 mutant causes enhanced production of rod photoreceptors in the absence of exogenous cytokines, whereas inhibiting ERK activation by a MEK (mitogen-activated protein kinase kinase)-specific inhibitor has no effect on rod photoreceptor differentiation in vitro. Furthermore, disrupting the function of epidermal growth factor (EGF) receptors, which modulate rod development in vivo, indicates that the EGF family of ligands does not mediate the inhibitory effect of cytokine on rod differentiation. These results demonstrate that cytokine signal transduction is dynamic and heterogeneous in the developing retina, and that endogenous ligand-induced STAT activation in retinal progenitor and/or photoreceptor precursor cells plays an important role in regulating photoreceptor development.

Animals↗