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Results for “Retinal Rod Photoreceptor Cells”

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At least 829 records · Page 46Linked to original sources
PubMed1998

Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa.

Ribozymes, catalytic RNA molecules that cleave a complementary mRNA sequence, have potential as therapeutics for dominantly inherited disease. Twelve percent of American patients with the blinding disease autosomal dominant retinitis pigmentosa (ADRP) carry a substitution of histidine for proline at codon 23 (P23H) in their rhodopsin gene, resulting in photoreceptor cell death from the synthesis of the abnormal gene product. Ribozymes can discriminate and catalyze the in vitro destruction of P23H mutant mRNAs from a transgenic rat model of ADRP. Here, we demonstrate that in vivo expression of either a hammerhead or hairpin ribozyme in this rat model considerably slows the rate of photoreceptor degeneration for at least three months. Catalytically inactive control ribozymes had less effect on the retinal degeneration. Intracellular production of ribozymes in photoreceptors was achieved by transduction with a recombinant adeno-associated virus (rAAV) incorporating a rod opsin promoter. Ribozyme-directed cleavage of mutant mRNAs, therefore, may be an effective therapy for ADRP and also may be applicable to other inherited diseases.

Animals↗
PubMed1999

Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae.

Mutations in the dystrophin gene cause muscular dystrophy as well as cognitive impairments, including an abnormal dark-adapted electroretinogram. To investigate the basis for the ocular phenotype, we analysed dystrophin and the dystrophin-associated protein beta-dystroglycan in retinae from mdx3Cv mice. This strain has a mutation in the dystrophin gene and abnormalities in the electroretinogram which are similar to those of muscular dystrophy patients. Despite an overall reduction of all dystrophin isoforms and of beta-dystroglycan in retinal tissue from mutant mice, we observed no apparent change in the histotypic layering of the retina, or in the ultrastructure of several specific cell types, including rods and cones. In retinae from wild type and mdx3Cv mice, dystrophin and beta-dystroglycan were concentrated in small extensions of rod and cone photoreceptor terminals protruding into the outer plexiform layer. Beta-dystroglycan but not dystrophin was also clustered around the inner limiting membrane and the capillary basal laminae. While the labelling pattern around the basal laminae was not altered in the mutant mice, we found that the area as well as the intensity of the dystrophin and beta-dystroglycan immunoreactivity associated with the terminals of rod photoreceptors were severely reduced. The same parameters were much less affected in cone terminals. These results show, that dystrophin and beta-dystroglycan are differentially distributed in the retina, and that a severe reduction of dystrophin has no gross effect on retinal structure, but could influence intraretinal signalling at the level of the photoreceptor terminals. Moreover, the mutation in mdx3Cv mice has a selective effect on rods, providing an explanation for the altered electroretinogram.

Animals↗
PubMedDate not supplied

Visual functional effects of constant blue light in a retinal degenerate rat model.

Retinal degenerative conditions increase susceptibility to light damage, but rapid retinal degeneration (RD) models show less susceptibility to cyclic dim light. We investigated whether constant blue light (BL) exposure can eliminate the residual visual responses in a comparatively rapid RD rat model. Pigmented rhodopsin mutant S334ter line-3 rat pups (21 days old) were exposed for 5-6 consecutive days to constant BL. Visual behavior was evaluated with an optokinetic head tracking apparatus. Electrophysiological recordings were made from the superior colliculus (SC). S-antigen, red-green opsin and rhodopsin immunoreactive residual photoreceptors were counted. Following BL exposure, head tracking was significantly reduced at 0.25 cycles degree(-1) in 38-day-old line 3 rats. With a 0.125 cycles degree(-1) stimulus, the head tracking performance of 80-day-old BL rats were similar to that of 220-day-old no-BL-treated line-3 rats. SC recordings also revealed a significant decrease in the residual photoreceptor activity. Histological evaluation showed reduction of the rod population in the central area of the light-damaged retina. Exposure to constant BL considerably reduces the residual visual responses in a rapid degenerating RD rat model.

Age Factors↗
PubMed1999

An immunohistochemical study of an autosomal dominant feline rod/cone dysplasia (Rdy cats).

An autosomal dominant, early onset feline model of rod/cone dysplasia has been described. The clinical features, light and electron microscopy, and the electrophysiology were documented. We have now examined in more detail the histopathological and immunohistochemical changes during the early phase of the disease using antibodies against opsin, synaptophysin, glial fibrillary acidic protein (GFAP) and an epithelial marker (MNF118). We have also demonstrated programmed cell death by a modified TUNEL (Terminal deoxynucleotidyl transferase, Uridine triphosphate, Nick End Labelling) technique. In the Rdy cats, there was significant photoreceptor degeneration between 5 and 17 weeks of age. The TUNEL-labeled cell and pyknotic cell counts in the outer nuclear layer peaked at around 9 weeks of age. Accumulation of opsin in the entire outer nuclear layer of the retina was noted with opsin-immunolabeled rod neurite sprouting. There was a reduction in synaptophysin immunoreactivity in the outer plexiform layer. The Muller cells were activated and expressed GFAP. No significant change of immunolabeling of MNF118 was found. These findings closely parallel those seen in human RP.

Animals↗
PubMed1997

Postmitotic cells fated to become rod photoreceptors can be respecified by CNTF treatment of the retina.

Lineage analyses of vertebrate retinae have led to the suggestions that cell fate decisions are made during or after the terminal cell division and that extrinsic factors can influence fate choices. The evidence for a role of extrinsic factors is strongest for development of rodent rod photoreceptors ('rods'). In an effort to identify molecules that may regulate rod development, a number of known factors were assayed in vitro. Ciliary neurotrophic factor (CNTF) was found to have a range of effects on retinal cells. Addition of CNTF to postnatal rat retinal explants resulted in a dramatic reduction in the number of differentiating rods. Conversly, the number of cells expressing markers of bipolar cell differentiation was increased to a level not normally seen in vivo or in vitro. In addition, a small increase in the percentage of cells expressing either a marker of amacrine cells or a marker of Muller glia was noted. It was determined that many of the cells that would normally differentiate into rods were the cells that differentiated as bipolar cells in the presence of CNTF. Prospective rod photoreceptors could make this change even when they were postmitotic, indicating that at least a subset of cells fated to be rods were not committed to this fate at the time they were born. These findings highlight the distinction between cell fate and commitment. Resistance to the effect of CNTF on rod differentiation occurred at about the time that a cell began to express opsin. The time of commitment to terminal rod differentiation may thus coincide with the initiation of opsin expression. In agreement with the hypothesis that CNTF plays a role in rod differentiation in vivo, a greater percentage of cells were observed differentiating as rod photoreceptors in mouse retinal explants lacking a functional CNTF receptor, relative to wild-type littermates.

Animals↗
PubMed1993

Photoreceptor damage following exposure to excess riboflavin.

Flavins generate oxidants during metabolism and when exposed to light. Here we report that the photoreceptor layer of retinas from black-eyed rats is reduced in size by a dietary regime containing excess riboflavin. The effect of excess riboflavin was dose-dependent and was manifested by a decrease in photoreceptor length. This decrease was due in part to a reduction in the thickness of the outer nuclear layer, a structure formed from stacked photoreceptor nuclei. These changes were accompanied by an increase in photoreceptor outer segment autofluorescence following illumination at 328 nm, a wavelength that corresponds to the excitation maxima of oxidized lipopigments of the retinal pigment epithelium.

Animals↗
PubMed1998

Rod pigment and rod noise in the European toad Bufo bufo.

Behavioural experiments and ganglion cell recordings indicate that the visual sensitivity of dark-adapted toads is limited by the occurrence of spontaneous isomerization-like noise events in the rods. The frequency of these "false photons" has previously been studied (with micropipette recording) in the toad species Bufo marinus, while the behavioural thresholds were determined using Bufo bufo toads. Thus, it was necessary to check that the noise event frequency is roughly the same in these two species. Here we show that it is, in both species, close to 0.02 events per second and rod (at 22 degrees C). Using microspectrophotometry we further show that the absorption spectra of these two rhodopsins are very similar, peaking around 503.3 and 501.8 nm for B. marinus and B. bufo, respectively.

Animals↗
PubMed2000

Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

Animals↗
PubMed2005

G-protein-coupled enzyme cascades have intrinsic properties that improve signal localization and fidelity.

G-protein-coupled enzyme cascades are used by eukaryotic cells to detect external signals and transduce them into intracellular messages that contain biological information relevant to the cell's function. Since G-protein-coupled receptors that are designed to detect different kinds of external signals can generate the same kind of intracellular response, effective signaling requires that there are mechanisms to increase signal specificity and fidelity. Here we examine the kinetic equations for the initial three stages in a generic G-protein-coupled cascade and show that the physical properties of the transduction pathway result in two intrinsic features that benefit signaling. 1), The response to a single activated receptor is naturally confined to a localized spatial domain, which could improve signal specificity by reducing cross talk. 2), The peak of the response generated by such a signaling domain is limited. This saturation effect reduces trial-to-trial variability and increases signaling fidelity by limiting the response to receptors that remain active for longer than average. We suggest that this mechanism for reducing response fluctuations may be a contributing factor in making the single photon responses of vertebrate retinal rods so remarkably reproducible.

Animals↗
PubMed1994

Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells.

The retinal bipolar cell receiving glutamate transmission from photoreceptors mediates a key process in segregating visual signals into ON center and OFF center pathways. This transmission involves a G protein-coupled metabotropic glutamate receptor (mGluR). Immunocytochemical and immunoelectron microscopic studies indicate that restricted localization of a specific mGluR subtype, mGluR6, at the postsynaptic site of the rat rod bipolar cell. This specialization is developmentally regulated: mGluR6 is initially distributed in both the soma and dendrites and is finally concentrated on the postsynaptic site. The mGluR6 localization is reversed when photoreceptors degenerate in the mutant rat with retinal dystrophy. Evidence is thus presented indicating specialized, developmentally regulated receptor distribution in the central nervous system and the crucial role of mGluR6 in photoreceptor-bipolar cell synaptic transmission.

Amino Acid Sequence↗
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↗
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↗