Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Retinal Rod Photoreceptor Cells”

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 847 records · Page 47Linked to original sources
PubMedDate not supplied

Transmission of single photon signals through a binary synapse in the mammalian retina.

At very low light levels the sensitivity of the visual system is determined by the efficiency with which single photons are captured, and the resulting signal transmitted from the rod photoreceptors through the retinal circuitry to the ganglion cells and on to the brain. Although the tiny electrical signals due to single photons have been observed in rod photoreceptors, little is known about how these signals are preserved during subsequent transmission to the optic nerve. We find that the synaptic currents elicited by single photons in mouse rod bipolar cells have a peak amplitude of 5-6 pA, and that about 20 rod photoreceptors converge upon each rod bipolar cell. The data indicates that the first synapse, between rod photoreceptors and rod bipolar cells, signals a binary event: the detection, or not, of a photon or photons in the connected rod photoreceptors. We present a simple model that demonstrates how a threshold nonlinearity during synaptic transfer allows transmission of the single photon signal, while rejecting the convergent neural noise from the 20 other rod photoreceptors feeding into this first synapse.

Animals↗
PubMed2003

GDNF regulates chicken rod photoreceptor development and survival in reaggregated histotypic retinal spheres.

PURPOSE: To investigate the role of glial-cell-line-derived neurotrophic factor (GDNF) on proliferation, differentiation, and apoptosis of different retinal cell types--in particular, photoreceptor cells. METHODS: Reaggregated histotypic spheres, derived from retinal cells of the E6 chicken embryo were used. Under rotation, so-called rosetted spheroids arose by aggregation of dissociated retinal cells, followed by the proliferation, migration, differentiation and programmed cell death of particular cell types. Rosetted spheroids were cultured under serum-reduced conditions, either in the absence or presence of 50 ng/mL GDNF. At appropriate stages, rosetted spheroids were analyzed by using conventional staining and immunolabeling with antibodies against different retinal cell types. RESULTS: At early stages of culture, the application of GDNF to rosetted spheroids significantly increased and sustained the rate of proliferation. In particular, a de novo production of rod photoreceptors was observed, whereas cone photoreceptors and amacrine, horizontal, ganglion, and Müller cells were not affected. In addition, in GDNF-treated cultures, rod photoreceptors differentiated earlier than in nontreated cultures. In older rosetted spheroids raised in absence of GDNF, rod but not cone photoreceptors underwent apoptosis. By supplementation with GDNF, the percentage of dying rod photoreceptors was dramatically reduced (31%-6% at 8 days in culture, 71%-3% at 10 days in culture). Both the mitogenic and survival promoting effect of GDNF were dose dependent. CONCLUSIONS: The results strongly suggest that GDNF, at least in vitro, affects rod photoreceptors. Depending on the developmental stage, GDNF regulates their proliferation, differentiation, and survival.

Animals↗
PubMed2002

A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina.

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca(2+) currents (I(Ca)) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca(2+) channels that regulate the release of L-glutamate. In the retina, adenosine is released in the dark when L-glutamate release is maximal. We tested whether adenosine inhibits I(Ca) and intracellular Ca(2+) increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I(Ca) and the [Ca(2+)]i increase evoked by depolarization in a dose-dependent manner with approximately 25% inhibition at 50 microM. An A2-selective agonist, (N(6)-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, (R)-N(6)-(1-methyl-2-phenylethyl)adenosine and N(6)-2-(4-aminophenyl)ethyladenosine, also inhibited I(Ca) and depolarization-induced [Ca(2+)]i increases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I(Ca) and the depolarization-evoked [Ca(2+)]i increase in rods. The results suggest that activation of A2 receptors stimulates PKA to inhibit L-type Ca(2+) channels in rods resulting in a decreased Ca(2+) influx that should suppress glutamate release.

Adenosine↗
PubMedDate not supplied

Mechanism of G-protein activation by rhodopsin.

Rhodopsin is a member of the family of G-protein-coupled receptors (GPCRs), and is an excellent molecular switch for converting light signals into electrical response of the rod photoreceptor cells. Light initiates cis-trans isomerization of the retinal chromophore of rhodopsin and leads to the formation of several thermolabile intermediates during the bleaching process. Recent investigations have identified spectrally distinguishable two intermediate states that can interact with the retinal G-protein, transducin, and have elucidated the functional sharing of these intermediates. The initial contact with GDP-bound G-protein occurs in the meta-Ib intermediate state, which has a protonated Schiff base as its chromophore. The meta-Ib intermediate in the complex with the G-protein converts to the meta-II intermediate with releasing GDP from the alpha-subunit of the G protein. Meta-II has a de-protonated Schiff base chromophore and induces binding of GTP to the alpha-subunit of the G-protein. Thus, the GDP-GTP exchange reaction, namely G-protein activation, by rhodopsin proceeds through at least two steps, with conformational changes in both rhodopsin and the G-protein.

Animals↗
PubMed1995

Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa.

Mutations in the genes encoding two proteins of the retinal rod phototransduction cascade, opsin and the beta subunit of rod cGMP phosphodiesterase, cause retinitis pigmentosa (RP) in some families. Here we report defects in a third member of this biochemical pathway in still other patients with this disease. We screened 94 unrelated patients with autosomal dominant RP and 173 unrelated patients with autosomal recessive RP for mutations in the gene encoding the alpha subunit of the rod cGMP-gated cation channel. Five mutant sequences cosegregated with disease among four unrelated families with autosomal recessive RP. Two of these were nonsense mutations early in the reading frame (Glu76End and Lys139End) and one was a deletion encompassing most if not all of the transcriptional unit; these three alleles would not be expected to encode a functional channel. The remaining two mutations were a missense mutation (Ser316Phe) and a frameshift [Arg654(1-bp del)] mutation truncating the last 32 aa in the C terminus. The latter two mutations were expressed in vitro and found to encode proteins that were predominantly retained inside the cell instead of being targeted to the plasma membrane. We conclude that the absence or paucity of functional cGMP-gated cation channels in the plasma membrane is deleterious to rod photoreceptors and is an uncommon cause of RP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Role of hyperpolarization-activated currents for the intrinsic dynamics of isolated retinal neurons.

The intrinsic dynamics of bipolar cells and rod photoreceptors isolated from tiger salamanders were studied by a patch-clamp technique combined with estimation of effective impulse responses across a range of mean membrane voltages. An increase in external K(+) reduces the gain and speeds the response in bipolar cells near and below resting potential. High external K(+) enhances the inward rectification of membrane potential, an effect mediated by a fast, hyperpolarization-activated, inwardly rectifying potassium current (K(IR)). External Cs(+) suppresses the inward-rectifying effect of external K(+). The reversal potential of the current, estimated by a novel method from a family of impulse responses below resting potential, indicates a channel that is permeable predominantly to K(+). Its permeability to Na(+), estimated from Goldman-Hodgkin-Katz voltage equation, was negligible. Whereas the activation of the delayed-rectifier K(+) current causes bandpass behavior (i.e., undershoots in the impulse responses) in bipolar cells, activation of the K(IR) current does not. In contrast, a slow hyperpolarization-activated current (I(h)) in rod photoreceptors leads to pronounced, slow undershoots near resting potential. Differences in the kinetics and ion selectivity of hyperpolarization-activated currents in bipolar cells (K(IR)) and in rod photoreceptors (I(h)) confer different dynamical behavior onto the two types of neurons.

Animals↗
PubMed2005

Predominant rod photoreceptor degeneration in Leber congenital amaurosis.

PURPOSE: An unusual retinal vascular morphology in an enucleated eye from a patient with Leber congenital amaurosis (LCA) has been associated with a mutation in AIPL1. The AIPL1 protein is expressed in the pineal gland and retinal photoreceptors. In the retina, AIPL1 is expressed in both developing cone and rod photoreceptors, but it is restricted to rod photoreceptors in the adult human retina. Therefore, this study was conducted to determine the photoreceptor phenotype in this LCA patient to determine if photoreceptors were differentially affected. METHODS: Additional genetic screening was performed and the consequences of the H82Y amino acid substitution characterized in an in vitro assay of NUB1 modulation. The morphology of the photoreceptors was examined by light and electron microscopy. Immunohistochemistry and immunofluorescent confocal microscopy was performed using a range of retinal photoreceptor markers. RESULTS: Transfection of the H82Y mutant AIPL1 in SK-N-SH cells revealed a normal subcellular localization and solubility but resulted in an increased ability of AIPL1 to redistribute GFP-NUB1 to the cytoplasm and resolve NUB1 fragment inclusion formation. Morphologically, the LCA retina appeared to be cone-dominant with a single layer of cone-like cells remaining in the central retina. Photoreceptor outer segments were absent and the surviving residual inner segments were severely shortened. Severe degeneration of the LCA retina was associated with upregulation of glial fibrillary acidic protein (GFAP). No signal was detected for AIPL1, rhodopsin, or L/M and S cone opsins in the LCA retina. Double labeling with peanut agglutinin (PNA) and wheat germ agglutinin (WGA) supported a cone-dominant phenotype for the surviving photoreceptors in the LCA retina, as did double labeling for cone arrestin, and rod and cone recoverin. The cone arrestin signal was restricted to the residual photoreceptor inner segments and was not detected in the cell bodies, axons, or axon terminals of the surviving photoreceptors. Recoverin immunoreactivity was most intense in the residual photoreceptor inner segments. CONCLUSIONS: The phenotype in this patient suggests that although AIPL1 is required for the development of normal rod and cone photoreceptor function, it might only be essential for rod and not cone survival in the adult.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.

Among the eight progressive neurodegenerative diseases caused by polyglutamine expansions, spinocerebellar ataxia type 7 (SCA7) is the only one to display degeneration in both brain and retina. We show here that mice overexpressing full-length mutant ataxin-7[Q90] either in Purkinje cells or in rod photoreceptors have deficiencies in motor coordination and vision, respectively. In both models, although with different time courses, an N-terminal fragment of mutant ataxin-7 accumulates into ubiquitinated nuclear inclusions that recruit a distinct set of chaperone/proteasome subunits. A severe degeneration is caused by overexpression of ataxin-7[Q90] in rods, whereas a similar overexpression of normal ataxin-7[Q10] has no obvious effect. The degenerative process is not limited to photoreceptors, showing secondary alterations of post-synaptic neurons. These findings suggest that proteolytic cleavage of mutant ataxin-7 and trans-neuronal responses are implicated in the pathogenesis of SCA7.

Animals↗
PubMed2005

Glycine modulates the center response of ON type rod-dominant bipolar cells in carp retina.

Effects of glycine on ON type rod-dominant bipolar cells (RBCs) were studied in isolated, superfused carp retina by intracellular recording technique and in carp retinal slice preparation by whole cell recording. Glycine of 4mM hyperpolarized RBCs and potentiated their light responses to large light spots, which was reversed by co-application of 10 microM strychnine. It was further found that illumination of the receptive field surround did not affect the depolarizing center response of RBCs. The above result therefore suggests that glycine modulates the center response of RBCs. Focal application of glycine to either dendrites or axon terminals of RBCs failed to induce any currents in both isolated cell and retinal slice preparations. On the other hand, glycine of 4mM increased the amplitude of the scotopic electroretinographic PIII component, which reflects the activity of rod photoreceptors. It seems likely that modulation by glycine of the RBC center response may be in part ascribed to a consequence of the potentiation of rod responses by glycine.

Animals↗
PubMed2000

Autosomal dominant cone-rod dystrophy due to a missense mutation (R838C) in the guanylate cyclase 2D gene (GUCY2D) with preserved rod function in one branch of the family.

We present the clinical and molecular genetic features of a large multi-generation Norwegian family with dominant cone-rod dystrophy. Ophthalmological evaluation including electroretinography showed cone dysfunction in younger patients, with rod dysfunction becoming apparent at more advanced stages of the disease. In one branch of the family, cone degeneration remained the only manifestation despite advancing age. Linkage analysis mapped the disease gene in this family to 17p12-p13, a chromosome region previously linked to cone-rod dystrophy in a Swedish family (CORD5). A maximum LOD score of 3.25 (straight theta = 0.00) for marker D17S1844 was obtained. Mutation analysis of the guanylate cyclase 2D gene (GUCY2D, MIM 600179, previously called RETGC1), located at 17p12-p13, showed a missense mutation (R838C) in exon 13, that co-segregated with the eye disease in the family. Our suspicion of the possibility of an interrelationship between the Swedish CORD5 family and the present family, both originating from Northern Scandinavia, initiated the linkage analysis in the Norwegian family. The R838C missense mutation was not, however, detected in the Swedish patients, strongly suggesting no relationship between these two families. The long-term ophthalmological evaluation in this large four-generation family, combined with the identification of the disease-causing mutation, provide critical information for refining the classification, prognosis, and genetic counselling of patients with cone-rod dystrophies.

Adult↗
PubMed2006

The CNTF/LIF signaling pathway regulates developmental programmed cell death and differentiation of rod precursor cells in the mouse retina in vivo.

Natural cell death is critical for normal development of the nervous system, but the extracellular regulators of developmental cell death remain poorly characterized. Here, we studied the role of the CNTF/LIF signaling pathway during mouse retinal development in vivo. We show that exposure to CNTF during neonatal retinal development in vivo retards rhodopsin expression and results in an important and specific deficit in photoreceptor cells. Detailed analysis revealed that exposure to CNTF during retinal development causes a sharp increase in cell death of postmitotic rod precursor cells. Importantly, we show that blocking the CNTF/LIF signaling pathway during mouse retinal development in vivo results in a significant reduction of naturally occurring cell death. Using retroviral lineage analysis, we demonstrate that exposure to CNTF causes a specific reduction of clones containing only rods without affecting other clone types, whereas blocking the CNTF/LIF receptor complex causes a specific increase of clones containing only rods. In addition, we show that stimulation of the CNTF/LIF pathway positively regulates the expression of the neuronal and endothelial nitric oxide synthase (NOS) genes, and blocking nitric oxide production by pre-treatment with a NOS inhibitor abolishes CNTF-induced cell death. Taken together, these results indicate that the CNTF/LIF signaling pathway acts via regulation of nitric oxide production to modulate developmental programmed cell death of postmitotic rod precursor cells.

Animals↗
PubMed2000

Analysis and quantitation of mRNAs encoding the alpha- and beta-subunits of rod photoreceptor cGMP phosphodiesterase in neonatal retinal degeneration (rd) mouse retinas.

The retinal degeneration(rd) mouse is a commonly-studied animal model of the family of human-inherited retinal blindness known as retinitis pigmentosa, and is a likely model in which therapies for these conditions will continue to be developed and tested. Mutation of the beta-subunit of the rod photoreceptor cell-specific cyclic GMP phosphodiesterase is known to cause photoreceptor apoptosis in these mice. However, the molecular phenotype of this mutation in terms of quantitative levels of the phosphodiesterase alpha- and beta-subunit messenger RNAs remains unknown. In this study, the expression of the alpha- and beta-phosphodiesterase subunits is compared in C57BL/6J +/+, rd /+, and rd / rd mouse retinas. Using the techniques of quantitative reverse transcription polymerase chain reaction and quantitative in situ hybridization, the expression of the subunit mRNAs was measured in retinas of postnatal mice 0-14 days of age. Additionally, full length coding sequences were amplified for both subunits, and the beta-phosphodiesterase subunit mRNA was further evaluated for evidence of alternative splicing. Lastly, a relative decrease in expression of the mutant beta-phosphodiesterase allele in rd /+ mice was observed.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Cosegregation of codon 807 mutation of the canine rod cGMP phosphodiesterase beta gene and rcd1.

PURPOSE: To determine if a previously reported nonsense mutation (G to A transition at nucleotide position 2420) in the canine rod cyclic GMP (cGMP) phosphodiesterase beta (PDEB) subunit gene cosegregates with the rod-cone dysplasia 1 disease allele (rcd1) in the rcd1-dog reference colony; to establish the prevalence of this mutation among rcd1-affected Irish setters in the United States; and to screen for this mutation in other forms of canine hereditary progressive retinal atrophy (PRA). METHODS: Exon 21 of canine PDEB, previously reported to contain a nonsense mutation in rcd1-affected dogs, was amplified by polymerase chain reaction from genomic DNA isolated from peripheral blood samples. The mutation was detected in amplified DNA by restriction enzyme digestion and double-stranded conformational polymorphism. Linkage between rcd1 and the PDEB mutation was tested using the computer program LIPED: RESULTS: Three different rcd1-informative canine pedigrees were tested for the PDEB nonsense mutation. The first was a multigenerational pedigree representing the rcd1 reference colony. The other two pedigrees represented purebred Irish setter breeding lines in which rcd1 was known to be segregating. In all three pedigrees, the same point mutation was present and segregated with no discordance with the rcd1 allele. Linkage analysis established a maximum logarithm of odds (LOD) score of 12.05 at a linkage distance (theta) of 0.0. In a representative sampling of Irish setters in the United States diagnosed clinically as affected with typical rcd1 phenotype, all dogs were demonstrated to have the same (codon 807) PDEB mutation. Three of four Irish setters affected with atypical, relatively slower disease also had this mutation, but one dog did not. This point mutation in the canine PDEB gene was absent in other forms of canine hereditary retinal degeneration. CONCLUSIONS: In three informative pedigrees, the codon 807 mutation in canine PDEB cosegregates with the rcd1 disease allele with zero discordance. A linkage distance (theta) of zero, with an LOD score of 12.05, indicates identity of this mutation and rcd1. This appears to be the only mutation causing rcd1 in the United States. In all other forms of canine hereditary retinal degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Iris degeneration tested (cd, erd, prcd, rcd2, X-linked PRA, and in one Irish setter with late onset PRA), this PDEB point mutation was absent.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Transmission of scotopic signals from the rod to rod-bipolar cell in the mammalian retina.

Mammals can see at low scotopic light levels where only 1 rod in several thousand transduces a photon. The single photon signal is transmitted to the brain by the ganglion cell, which collects signals from more than 1000 rods to provide enough amplification. If the system were linear, such convergence would increase the neural noise enough to overwhelm the tiny rod signal. Recent studies provide evidence for a threshold nonlinearity in the rod to rod bipolar synapse, which removes much of the background neural noise. We argue that the height of the threshold should be 0.85 times the amplitude of the single photon signal, consistent with the saturation observed for the single photon signal. At this level, the rate of false positive events due to neural noise would be masked by the higher rate of dark thermal events. The evidence presented suggests that this synapse is optimized to transmit the single photon signal at low scotopic light levels.

Amacrine Cells↗
PubMed1984

Further evidence that the survival of irradiated mammalian cells is controlled by temporal processes.

Theories of mammalian cellular radiosensitivity that exclude metabolic modification of radiation damage are untenable (Nagasawa et al., 1980). Evidence supporting that conclusion has been obtained from experiments with a radiosensitive, proliferating cell, the S/S variant of the L5178Y murine leukaemic lymphoblast, and a radioresistant, nondividing cell, the retinal photoreceptor (rod) of the rabbit. When S/S cells (mid-) G1 + 8 h in the cycle, at the peak of radioresistance, were X-irradiated at 37 degrees C and then treated hyperthermically (12 h, 38.7-40.3 degrees C), the survival curve, which has a shoulder at 37 degrees C, changed progressively to the simple exponential obtained for G1 cells. Under conditions where Ne ions (LET = 35 keV microns-1) have a relative biological effectiveness (RBE) of approximately 2 for normally radioresistant cells in vitro and in situ, the RBE for G1 S/S cells was approximately 1. Neon ions (1-50 Gy) caused similar amounts of DNA damage in S/S cells and photoreceptors, but the cellular responses were very different. After 5 Gy, the surviving fraction of asynchronous S/S cells was 10(-5), DNA structures were not restored and by 8 h post-irradiation extensive DNA degradation was evident; in the retina, however, the photoreceptor complement was unchanged for greater than 1 year, DNA structures appeared to be restored and remained so (many months) until late DNA degradation began. These phenomena can be explained satisfactorily only if temporal processes play a significant role in cellular radiosensitivity.

Animals↗
PubMed2004

Inner retinal photoreceptors (IRPs) in mammals and teleost fish.

Research over the past decade has provided overwhelming evidence that photoreception in the vertebrate eye is not confined to the rods and cones. The discovery of non-rod, non-cone ocular photoreceptors in mammals and fish arose from quite different lines of investigation. In transgenic mice entirely lacking functional rod and cone photoreceptors a range of responses to light, including the regulation of the circadian system and a pupillary light reflex, are preserved. Electrophysiological and imaging approaches were then able to characterise a coupled plexus of directly light sensitive ganglion cells. Most recently action spectroscopy has shown that a novel 'blue-light' sensitive photopigment based upon opsin/vitamin A (OP480) mediates these responses to light. Several candidate genes have emerged for OP480, with melanopsin being by far the strongest. A definitive link, however, between this gene and OP480 has still to be established. In contrast to the mammals, the discovery of inner retinal photoreceptors (IRPs) in fish started with the discovery of a new gene family (VA opsin). The teleost VA opsins form functional photopigments and are expressed in several different types of inner retinal neuron, including retinal horizontal cells. Recent studies have investigated the electrical properties of these photosensitive neurones, but their light-sensing role remains a matter of speculation. Thus the study of IRP is developing along quite separate lines. In the mammals the research is directed towards a molecular identification of the photopigment (OP480) and its cascade, whilst in fish the major effort is directed towards identifying a role for these novel photoreceptors using physiological approaches. The discovery of IRPs in the vertebrates tells us that despite 150 years of research, we still have much to learn about how the eye processes light.

Animals↗
PubMed1998

Post-Golgi trafficking of rhodopsin in retinal photoreceptors.

Rod outer segment renewal in retinal rod photoreceptors is mediated by polarised sorting of rhodopsin, and its associated proteins and lipids, on post-Golgi vesicles that bud from the trans-Golgi network and fuse with the specialised domain of the plasma membrane in the rod inner segment. This domain surrounds the cilium that connects the inner segment and the rod outer segment to which mature rhodopsin is delivered. The intracellular sorting machinery that regulates budding, targeting and fusion of rhodopsin carrier vesicles has been studied using multiple means including a newly developed cell-free assay that reconstitutes vesicle budding. These studies have revealed an essential role for small GTP-binding protein rab6, as well as the carboxyl-terminal domain of rhodopsin, in the formation of post-Golgi vesicles. In this report their role in post-Golgi trafficking of rhodopsin and the maintenance of photoreceptor cell polarity and health is discussed.

Animals↗