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Results for “Retinal Horizontal Cells”

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PubMed1999

The feedback pathway from horizontal cells to cones. A mini review with a look ahead.

The feedback pathway from HCs to cones forms the basis of the surround responses of the bipolar cells and is essential for the spectral opponency of horizontal cells. The nature of this feedback pathway is an issue of debate. Three hypothesis are presented in literature: (1) a GABAA-ergic feedback pathway; (2) a GABA-independent feedback pathway that modulates the Ca-current in cones; and (3) an electrical feedback pathway. In this review the evidence for the various pathways will be discussed. The conclusion is that the available evidence favors the hypothesis that feedback modulates the Ca-current in the cones in a GABA independent way. An alternative role of GABA in the outer plexiform layer is discussed and finally the functional consequences of the negative feedback pathway from horizontal cells to cones are presented.

Animals↗

PubMedDate not supplied

Cobalt ions inhibit negative feedback in the outer retina by blocking hemichannels on horizontal cells.

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co2+ block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co2+ on the cone/horizontal network of goldfish retina and found that Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca2+ current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca2+ current in cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co2+ are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.

Animals↗

PubMed2001

Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk.

The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive loss of rod and cone photoreceptors. We recently used positional cloning to demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy) locus of the RCS rat. In the present study, we sought to determine whether gene transfer of Mertk to a RCS rat retina would result in correction of the RPE phagocytosis defect and preservation of photoreceptors. We used subretinal injection of a recombinant replication-deficient adenovirus encoding rat Mertk to deliver the gene to the eyes of young RCS rats. Electrophysiological assessment of animals 30 days after injection revealed an increased sensitivity of treated eyes to low-intensity light. Histologic and ultrastructural assessment demonstrated substantial sparing of photoreceptors, preservation of outer segment structure, and correction of the RPE phagocytosis defect in areas surrounding the injection site. Our results provide definitive evidence that mutation of Mertk underlies the RCS retinal dystrophy phenotype, and that the phenotype can be corrected by treatment of juvenile animals. To our knowledge, this is the first demonstration of complementation of both a functional cellular defect (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE. These results, together with the recent discovery of MERTK mutations in individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as a model for gene therapy of diseases that arise from RPE dysfunction.

Adenoviridae↗

PubMed2004

Multiple spatiotemporal patterns of dendritic Ca2+ signals in goldfish retinal amacrine cells.

Although it has been reported that dendritic neurotransmitter releases from amacrine cells are regulated by the intracellular Ca(2+) concentration ([Ca(2+)](i)), their spatiotemporal patterns are not well explained. Fast Ca(2+) imagings of amacrine cells in the horizontal slice preparation of goldfish retinas under whole-cell patch-clamp recordings were undertaken to better investigate the spatiotemporal patterns of dendritic [Ca(2+)](i). We found that amacrine cell dendrites showed inhomogeneous [Ca(2+)](i) increases in both Na(+) spiking cells and cells without Na(+) spikes. The spatiotemporal properties of inhomogeneous [Ca(2+)](i) increases were classified into three patterns: local, regional and global. Local [Ca(2+)](i) increases were observed in very discrete regions and appeared as discontinuous patches, presumably evoked by local excitatory postsynaptic potentials. Regional [Ca(2+)](i) increases were observed in either a single or a small number of dendrites, presumably reflecting the result of dendritic action potentials. Global [Ca(2+)](i) increases were observed in the entire dendrites of a cell and were mediated by Na(+) action potentials or multiple Na(+) action potentials riding on slow depolarization. Ca(2+)-mediated potentials also evoked global [Ca(2+)](i) increase in cells without Na(+) spikes. These spatiotemporal dynamics of dendritic Ca(2+) signals may reflect multiple modes of synaptic integration on the dendrites of amacrine cells.

Action Potentials↗

PubMed2001

Structure and functional connections of presynaptic terminals in the vertebrate retina revealed by activity-dependent dyes and confocal microscopy.

The fluorescent dyes sulforhodamine 101 (SR 101) and FM1-43 were used as activity-dependent dyes (ADDs) to label presynaptic terminals in the retinas of a broad range of animals, including amphibians, mammals, fish, and turtles. The pattern of dye uptake was studied in live retinal preparations by using brightfield, fluorescence, and confocal microscopy. When bath-applied to the retina-eyecup, these dyes were avidly sequestered by the presynaptic terminals of virtually all rods, cones, and bipolar and amacrine cells; ganglion cell dendrites and horizontal cells lacked significant dye accumulation. Other structures stained with these dyes included pigment epithelial cells, cone outer segments, and Müller cell end-feet. Studies of dye uptake in dark- and light-adapted preparations showed significant differences in the dye accumulation pattern in the inner plexiform layer (IPL), suggesting a dynamic, light-modulated control of endocytotic activity. Presynaptic terminals in the IPL could be segregated on the basis of volume: bipolar varicosities in the IPL were typically larger than those of amacrine cells. The combination of retrograde labeling of ganglion cells and presynaptic terminal labeling with ADDs served as the experimental preparation for three-dimensional reconstruction of both structures, based on dual detector, confocal microscopy. Our results demonstrate a new approach for studying synaptic interactions in retinal function. These findings provide new insights into the likely number and position of functional connections from amacrine and bipolar cell terminals onto ganglion cell dendrites.

Adaptation, Ocular↗

PubMedDate not supplied

Activation of group II metabotropic glutamate receptors inhibits glutamate release from salamander retinal photoreceptors.

We investigated the effects of group II metabotropic glutamate receptor (mGluR) activation on excitatory synaptic transmission in the salamander retinal slice preparation. The group II selective agonists DCG-IV and LY354740 reduced light-evoked excitatory postsynaptic currents (EPSCs) in ganglion cells. To determine the synaptic basis of this effect, we also recorded from bipolar cells and horizontal cells. In ON bipolar cells, DCG-IV increased the inward current in darkness but did not affect the peak current at light onset. In OFF bipolar cells and horizontal cells, DCG-IV had the opposite effect, reducing the inward current in darkness. Given the opposite polarities of these two classes of synapses, our results suggest that group II mGluRs act presynaptically to reduce glutamate release from photoreceptors. To determine whether DCG-IV affected rods or cones, we applied light stimuli that selectively activate each type of photoreceptor. In horizontal cells, most of which receive mixed synaptic input from rods and cones, DCG-IV reduced rod-driven EPSCs evoked by 470-nm stimuli and cone-driven EPSCs elicited by 700-nm stimuli in the presence of a rod-saturating background. Thus, activation of group II mGluRs reduced rod- and cone-mediated glutamate release. Our results suggest that group II mGluRs could mediate feedback by which extracellular glutamate inhibits glutamate release from photoreceptor terminals.

Ambystoma↗

PubMed2006

A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa.

PURPOSE: To characterize the course of retinal disease in X-linked progressive retinal atrophy 2 (XLPRA2), a canine model of early onset X-linked retinitis pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15. METHODS: The retinas of 25 XLPRA2-affected dogs (age range, 2-40.6 weeks) and age-matched control subjects were collected, fixed, and embedded in epoxy resin for morphologic evaluation or in optimal cutting temperature (OCT) medium for TUNEL assay and immunohistochemistry. Cell-specific antibodies were used to examine changes in rods and cones and to evaluate the effects of the primary photoreceptor degeneration on inner retinal cells. RESULTS: Abnormal development of photoreceptors was recognizable as early as 3.9 weeks of age. Outer segment (OS) misalignment was followed by their disorganization and fragmentation. Reduction in length and broadening of rod and cone inner segments (IS) was next observed, followed by the focal loss of rod and cone IS at later time points. The proportion of dying photoreceptors peaked at approximately 6 to 7 weeks of age and was significantly reduced after 12 weeks. In addition to rod and cone opsin mislocalization, there was early rod neurite sprouting, retraction of rod bipolar cell dendrites, and increased Müller cell reactivity. Later in the course of the disease, changes were also noted in horizontal cells and amacrine cells. CONCLUSIONS: XLPRA2 is an early-onset model of XLRP that is morphologically characterized by abnormal photoreceptor maturation followed by progressive rod-cone degeneration and early inner retina remodeling. The results suggest that therapeutic strategies for this retinal degeneration should target not solely photoreceptor cells but also inner retinal neurons.

Animals↗

PubMed1992

Feedback connections and operation of the outer plexiform layer of the retina.

The primary feedback control apparatus in the outer retina is the sign-inverting feedback synapse between horizontal cells and cones. In many lower vertebrates horizontal cells release GABA in darkness, which opens Cl- channels in cones. Input-output relations of the feedback synapse reveal that the synaptic gain is light-dependent with the highest negative gain near the dark horizontal cell potential. The horizontal cell-cone feedback synapse improves the reliability of the photoreceptor output synapses. It also modulates the dynamic range and mediates color opponency and surround responses in second-order retinal neurons.

Animals↗

PubMed1997

Cortical dynamics.

Our ability to interpret visual scenes involves assembling the components of objects into a unified percept and segregating them from background, storing information about earlier visual experiences and testing our interpretations of the visual world against incoming sensory input. The influences of context, experience and expectation are reflected in the response properties of cells at early stages in the visual pathway. The responses of cells in primary visual cortex depend not only on the attributes of features lying within the classical receptive field but also on the global characteristics of the contours and surfaces within which these features are embedded. The substrate for lateral interactions includes a plexus of long-range horizontal connections within each cortical area that links columns of similar orientation specificity and cells with widely separated receptive fields. The horizontal connections also play a role in the plasticity of receptive field structure and of cortical functional architecture, induced over long time scales by retinal lesions and over short time scales by patterned visual stimulation. The long-term changes are associated with synaptogenesis; and the short-term changes with an increase in synaptic effectiveness. The dynamics of cortical function persist throughout adulthood and are general to all cortical areas, including primary sensory cortices.

Animals↗

PubMed1988

Retinal topography in reef teleosts. I. Some species with well-developed areae but poorly-developed streaks.

The retinal ganglion cell layer of five species of teleosts has been studied from Nissl-stained whole-mounts and the distribution of neuronal elements determined quantitatively. Isodensity contour maps of neurons in the ganglion cell layer revealed areas of high density (areae centrales) predominantly in the temporal retina, but other areae were also found in the nasal and dorso-nasal retina. Neuronal densities within the ganglion cell layer at the areae centrales ranged from 0.4 x 10(4) to 4.7 x 10(4) cells/mm2. Species that were found to lack a horizontal streak of high ganglion cell density appear to be those whose behaviour suggests they possess an interrupted view of the sand-water horizon and are 'enclosed' species. Concentric density contours around an area centralis seem to be associated with enclosed environments. The relationship between retinal topography and niche is also discussed.

Animals↗

PubMed2003

Dynamics of sensitivity regulation in primate outer retina: the horizontal cell network.

The goal of these experiments was to define the time course and degree of cone adaptation in primate outer retina by use of probe stimuli upon temporally modulated backgrounds. Recordings were obtained from primate horizontal cells. Test probes were either a low-amplitude, high-frequency sinusoid superimposed on a slowly modulated background or small test pulses superimposed on backgrounds of various frequencies. The amplitude of the test response was modulated by the background, indicating sensitivity regulation. Results were consistent with gain controls which, at 1000 td, required approximately 10-20 ms to completion. These mechanisms could also account for some of the distortions of horizontal cell responses to sinusoids and pulses. Modulation of test responsivity occurred at low background contrasts, suggesting no threshold change in light level must be exceeded to evoke sensitivity regulation. As retinal illuminance increased from darkness, sensitivity regulation was evident at 10-20 td.

Adaptation, Ocular↗

PubMed1991

Biocytin: intracellular staining, dye-coupling and immunocytochemistry in carp retina.

Correlation of electrophysiological and morphological, including ultrastructural, characteristics of neurones is important for understanding the functional organization of neuronal systems. Further correlation with neurotransmitter content is essential for determining the neurochemical(s) used by a given neurone for propagating its signal. The two main neuronal markers presently available (lucifer yellow and horseradish peroxidase) are not satisfactory for correlating all three aspects. We have devised a new simple procedure whereby retinal interneurones can be labelled with biocytin by positive ionophoresis of an unbuffered solution. Biocytin readily crosses gap junctions thus revealing extensive networks of coupled cells. In the case of H1 horizontal cells, which are known to be GABAergic, the neurotransmitter can also be demonstrated by superimposed immunocytochemistry.

Animals↗

PubMed1998

Changes in NADPH-diaphorase expression induced by excitotoxicity in the goldfish retina: relation with some morphological and biochemical aspects.

We report alterations in the pattern of NADPH-diaphorase staining, a marker of nitric oxide, in the goldfish retina after kainic acid administration. The heavily stained ellipsoids of the photoreceptors, the heavily stained neurons of the inner plexiform layer and the labeled neurons of the ganglion cell layer are spared by excitotoxic insult, while the faintly medium sized neurons of the inner plexiform layer disappear after kainic acid administration. Furthermore, in the bipolar and in the horizontal retinal neurons we observe an induction of NADPH-diaphorase expression. The kainic acid-induced neurotoxicity evaluated by morphological observations and by measuring the levels of choline acetyltranferase in retinal homogenates, is not prevented by the administration of a nitric oxide synthase inhibitor.

Animals↗

PubMed1986

An ultrastructural study of embryonic chick retinal neurons in culture.

The differentiation of cells and synapses in explants of 9-day-old chick embryo retina has been studied by light and electron microscopy over a period of 35 days in vitro, and samples of retina from the 9-day chick foetus were directly fixed and prepared for study. At the time of explantation the retinae were poorly differentiated and no lamination was apparent. From day 14 onwards, outer and inner nuclear layers (ONL, INL) separated by a layer of neuropil corresponding to the outer plexiform layer (OPL) and a layer of scattered large ganglion cells separated from the INL by a zone of neuropil resembling the inner plexiform layer (IPL) were apparent, and a well-differentiated outer limiting membrane was established close to the surface of the explants. In the oldest cultures some development of photoreceptor outer segments occurred but a distinct optic nerve fibre layer did not form. Although cell identification presented problems even in the oldest cultures, the major retinal cell types described in vivo could be identified. Photoreceptor cells developed pedicles in the OPL which became filled with synaptic vesicles and synaptic ribbons and established ribbon synapses (including triads) with and were commonly invaginated by processes from horizontal and bipolar cells. Processes of bipolar cells in the IPL formed simple and dyad synapses. At least two types of presynaptic amacrine cells were also identified in the INL, one of which contained large numbers of dense-core vesicles. The ganglion cells, though sparse, were large and well differentiated. These findings show that all the major neuronal types of the retina are capable of developing and differentiating in vitro, lagging behind the time-table of development and differentiation in vivo by approximately 7 days, but resulting in a histotypically organised retina with synaptic neuropil showing many similarities to the corresponding neuropil in vivo.

Animals↗

PubMed1980

A second type of horizontal cell in the monkey retina.

A second type of horizontal cell with a distinctly different appearance from the previously known horizontal cell has been seen in Golgi-impregnated monkey retinas. The new HII cell has a different dendritic branching pattern from the commonly described HI cell type, and it has a short convoluted axon with collaterals bearing small clusters of terminals. Comparisons of the two cell types at different retinal eccentricities show that HII cells have larger dendritic trees than HI cells in the foveal region but smaller dendritic trees than HIs in peripheral retina. Dendritic terminals of the new HII cell, like the HI cell, contact cone pedicles as lateral elements of the ribbon synapses. The isolated terminals or clusters of terminals borne by the short axon of the HII cell also contact cone pedicles as lateral elements rather than contacting rod spherules as lateral elements like HI terminal arborizations. Thus, the monkey like other vertebrates has at least two horizontal cell types which differ in morphology and synaptic connections.

Animals↗

PubMed1992

The effect of simultaneous internal tamponade on fluid compartmentalization and its relationship to cell proliferation.

To determine whether the residual free spaces within the vitreous chamber that result after vitreoretinal surgery and internal tamponade may be avoided, and to verify whether such compartmentalization is of real importance in the recurrence of postoperative proliferative vitreoretinopathy (PVR), the use of simultaneous double filling with polydimethylsiloxane (PDMS) and fluorosilicone (FSiO) in the repair of complicated retinal detachment is evaluated in 12 selected cases. Initial retinal reattachment was achieved in all cases. PVR recurred in 10 patients (83%), 6 of whom showed partial retinal detachment. Inferior and superior postoperative residual free spaces were abolished by this procedure, but a new residual fluid space was created, lying horizontally between the bubbles and expanding in a triangular shape nasal to the optic disc and temporal to the macula. Overall, 9 of 10 eyes with PVR after surgery had proliferation involving these areas. These findings support the concept that compartmentalization is of major importance in determining postoperative cell proliferation.

Adult↗

PubMed1992

Spatial density and immunoreactivity of bipolar cells in the macaque monkey retina.

The anatomical substrates of spatial and color vision in the primate retina are investigated by measuring the immunoreactivity and spatial density of bipolar, amacrine and horizontal cells in the inner nuclear layer of the macaque monkey retina. Bipolar cells can be distinguished from amacrine and horizontal cells by their differential immunoreactivity to antisera against glutamate, glycine, GABA, parvalbumin, calbindin (CaBP D-28K), and the L7 protein from mouse cerebellum. The spatial density of bipolar cells is compared to the densities of photoreceptors and ganglion cells at different retinal eccentricities. In the centralmost 2 mm, cone bipolar cells outnumber ganglion cells by about 1.4:1. The density of cone bipolar cells is thus high enough to allow for input to different (parasol and midget) ganglion cell classes by different (diffuse and midget) bipolar cell classes. The density gradient of cone bipolar cells follows closely that of ganglion cells in central retina but falls less steeply in peripheral retina. This suggests that the convergence of cone signals to the receptive fields of ganglion cells in the peripheral retina occurs in the inner plexiform layer. The density of cone bipolar cells is 2.5-4 times that of cones at all eccentricities studied, implying that cone connectivity to bipolar cells remains constant throughout the retina. Different subgroups of bipolar cells are distinguished by their relative immunoreactivity to the different antisera. All rod and cone bipolar cells show moderate to strong glutamate-like immunoreactivity. The bipolar cells that show weak to moderate GABA-like immunoreactivity are also labeled with the antiserum to the L7 protein and are thus identified as rod bipolar cells. Nearly half of all cone bipolar cells showed glycine-like immunoreactivity. The results suggest that the inhibitory neurotransmitter candidates GABA and glycine are segregated respectively in rod and cone bipolar cell pathways. A diffuse, cone bipolar cell type can be identified by the anti-parvalbumin and the anti-calbindin antisera. All horizontal cells show parvalbumin-like immunoreactivity. Nearly all amacrine cells show GABA-like or glycine-like immunoreactivity; a variety of subpopulations also show immunoreactivity to one or more of the other markers used.

Animals↗

PubMed1999

The dopamine D2 receptor subfamily in rat retina: ultrastructural immunogold and in situ hybridization studies.

Dopamine, a major neurotransmitter in the vertebrate retina, is released from interplexiform cells and a restricted subset of amacrine cells. Dopamine effects vary between different retinal cell types, most likely due to differences in cell-specific receptor subtype expression. Identification of cells expressing receptors of the D2-subfamily (D2R, D3R, D4R) on a light microscopical level has rendered equivocal results, and no information is as yet available concerning the subcellular distribution of receptor protein. In the present study, D2R and D2/3R subtype-specific antisera, and D2R-, D3R- and D4R-specific oligonucleotide probes were used for ultrastructural and in situ hybridization analyses of the receptor subtype distribution in the rat retina. Light and electron microscopy showed that in addition to the known localization of intense D2R-immunoreactivity in all dopaminergic cells immunoreactive for tyrosine hydroxylase (TH), homogeneous, less intense D2R-immunoreactivity was also seen throughout the inner plexiform layer (IPL). Ultrastructurally, many additional amacrine cell processes devoid of TH-immunoreactivity at all levels of the inner plexiform layer were immunoreactive. D2R-immunoreactivity was found mainly on intracellular vesicles, and immunoreactivity associated with the plasma membrane was always extrasynaptic. No D2R-immunoreactivity was found in amacrine cell somata postsynaptic to the so-called dopaminergic 'ring endings'. Many D2R-mRNA reactive cells were observed throughout the inner nuclear layer. Morphologically, labelled cells resemble amacrines and bipolars but not horizontal cells. Reactivity with splice variant-specific oligonucleotide probes suggested that the D2LR variant is the predominant if not the only D2R isoform in the rat retina. D2R-mRNA reactivity was not observed in other retinal layers, in particular not in photoreceptor inner segments, which displayed D4R-mRNA reactivity. D3R-mRNA reactivity was not detected. The results indicate that D2-like responses are mediated through the D2R subtype, by an autoreceptor mechanism in dopaminergic cells, and by volume transmission in non-dopaminergic cells of the inner retina. D2-like responses in photoreceptors probably represent D4R activation.

Animals↗