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PubMed2003

Increased activity of cyclooxygenase-2 signals early neurodegenerative events in the rat retina following transient ischemia.

Following transient retinal ischemia, there is neuronal cell death, breakdown of the blood-retinal barrier, activation of microglia and infiltration by hematogenous cells. The early appearance of cyclooxygenase-2 (COX-2) following an ischemic event may be responsible for signaling some of the responses that lead to neurodegeneration. We have determined the time courses of changes in protein levels and cellular localizations of COX-2 in the rat retina after transient ischemia. In the normal rat retina, COX-2 immunoreactivity was present in neurons in the INL and ganglion cell layer (GCL). Six to 12 hr after ischemia, COX-2 immunoreactivity was upregulated/induced in horizontal cells, amacrine cells, retinal ganglion cells, displaced amacrine cells of the INL and GCL, and Müller cells. The NMDA-receptor antagonist, MK801, blocked the increased COX-2 protein level and COX-2 immunoreactivity in neurons of the INL and GCL, but did not affect the induction of COX-2 in Müller cells after ischemia. The selective COX-2 inhibitor, SC-58236, prevented apoptotic cell death and was neuroprotective against loss of retinal ganglion cells after ischemia. Following transient ischemia, the selective COX-2 inhibitor did not prevent breakdown of the blood-retinal barrier or activation of microglia. However, the selective COX-2 inhibitor reduced infiltration of hematogenous cells into the retina. These results suggest that the early, increased activity of COX-2 signals neurodegenerative events following retinal ischemia.

Animals↗
PubMed2002

Cellular localization of cyclooxygenase-1 and cyclooxygenase-2 in the normal mouse, rat, and human retina.

Prostaglandins, synthesized by cyclooxygenase (COX), regulate diverse neurophysiological actions such as regulation of autonomic responses, transmission of pain, generation of fever, control of sleep-wake cycle, synaptic signaling, and cross-talk between neurons and glia in the central nervous system. Although prostaglandins have been widely studied in the anterior segment tissues of the eye, relatively little is known about prostaglandins in the neural retina. By using immunohistochemistry, we have compared the cellular expression and localization of COX-1 and COX-2 in the normal mouse, rat, and human retina. In the normal mouse retina, COX-1 immunoreactivity is present in the outer segments of photoreceptor cells, horizontal cells, microglia, retinal ganglion cells, and displaced amacrine cells. In the normal rat retina, COX-1 immunoreactivity is present in microglia, retinal ganglion cells, and displaced amacrine cells. In the normal human retina, COX-1 immunoreactivity is present in microglia, astrocytes, retinal ganglion cells, and displaced amacrine cells. In the normal mouse and rat retina, COX-2 immunoreactivity is present in processes of the outer plexiform layer and in certain amacrine cells and retinal ganglion cells. In the normal human retina, COX-2 immunoreactivity is only present in processes of the outer plexiform layer. These results suggest that prostaglandins, synthesized by COX-1 or COX-2, may contribute to normal physiological and homeostatic functions in the retina.

Amacrine Cells↗
PubMed1994

Functional coupling of a Ca2+/calmodulin-dependent nitric oxide synthase and a soluble guanylyl cyclase in vertebrate photoreceptor cells.

Electrophysiological recordings on retinal rod cells, horizontal cells and on-bipolar cells indicate that exogenous nitric oxide (NO) has neuromodulatory effects in the vertebrate retina. We report here endogenous NO formation in mammalian photoreceptor cells. Photoreceptor NO synthase resembled the neuronal NOS type I from mammalian brain. NOS activity utilized the substrate L-arginine (Km = 4 microM) and the cofactors NADPH, FAD, FMN and tetrahydrobiopterin. The activity showed a complete dependence on the free calcium concentration ([Ca2+]) and was mediated by calmodulin. NO synthase activity was sufficient to activate an endogenous soluble guanylyl cyclase that copurified in photoreceptor preparations. This functional coupling was strictly controlled by the free [Ca2+] (EC50 = 0.84 microM). Activation of the soluble guanylyl cyclase by endogenous NO was up to 100% of the maximal activation of this enzyme observed with the exogenous NO donor compound sodium nitroprusside. This NO/cGMP pathway was predominantly localized in inner and not in outer segments of photoreceptors. Immunocytochemically, we localized NO synthase type I mainly in the ellipsoid region of the inner segments and a soluble guanylyl cyclase in cell bodies of cone photoreceptor cells. We conclude that in photoreceptors endogenous NO is functionally coupled to a soluble guanylyl cyclase and suggest that it has a neuromodulatory role in visual transduction and in synaptic transmission in the outer retina.

Amino Acid Oxidoreductases↗
PubMed2003

Models describing nonlinear interactions in graded neuron synapses.

An intracellular recording made from the retinal luminosity horizontal cell (LHC) demonstrated that repetitive red flashes enhanced the cell's responsiveness to red stimulus and depressed its responsiveness to green stimulus and that repetitive green flashes suppressed the cell's red response but produced little change in its green response. Based on the idea that the spectral plasticity of LHCs may reflect some synaptic efficacy changes between the LHC and various cones, a self-organizing system is proposed to investigate the possible manner of information processing and storage within the synapses. The results of model analysis suggest that the stimulus-pattern-related spectral plasticity is attributable to the excitatory interaction within the same kinds of synapses and the inhibitory interaction between different kinds of synapses. This system is able to encode and store the history of signal transmission in a graded and cumulative fashion.

Animals↗
PubMed2001

Modulation of a voltage-gated calcium channel linked to activation of glutamate receptors and calcium-induced calcium release in the catfish retina.

1. Catfish (Ictalurus punctatus) retinal cone horizontal cells contain an L-type calcium current that has been proposed to be involved in visual processing. Here we report on the modulation of this current by activation of glutamate receptors and calcium-induced calcium release (CICR) from intracellular calcium stores. 2. Fluorescence data obtained from isolated horizontal cells loaded with indo-1 provided evidence of calcium release from an intracellular calcium store sensitive to caffeine, calcium and ryanodine. In the presence of caffeine, ryanodine-sensitive stores released calcium in a transient manner. Release of calcium was blocked when cells were preincubated in BAPTA, in the presence of ruthenium red, or in low concentrations of ryanodine. 3. The release of calcium from ryanodine-sensitive stores directly corresponded with a decrease of the voltage-gated L-type calcium current amplitude. Caffeine-induced modulation of the calcium current was reduced in the presence of ruthenium red. 4. Activation of ionotropic kainate receptors on catfish cone horizontal cells triggered CICR from ryanodine-sensitive stores and mimicked inhibition of the voltage-gated calcium current. Kainate-induced inhibition of the calcium current was diminished when intracellular calcium stores were inhibited with ruthenium red or depleted with ryanodine, or when calmodulin antagonists or CaM kinase II inhibitors were present. 5. These results provide evidence that activation of an ionotropic glutamate receptor on catfish cone horizontal cells is linked to calcium release from ryanodine-sensitive intracellular calcium stores and modulation of the L-type calcium current activity. Inhibition of this calcium current directly or indirectly involves calmodulin and CaM kinase II and represents a possible mechanism used by horizontal cells to affect response properties of these cells.

Animals↗
PubMed1975

Horizontal cells in cat retina with independent dendritic systems.

Cat horizontal cells are retinal neurons with two functionally distinct parts: the cell body receives signals predominantly from cones, while the terminal arborization receives predominantly from rods. The long thin process connecting these parts neither generates impulses nor allows significant passive electrotonic conduction between them.

Animals↗
PubMed1989

Displaced horizontal cells and biplexiform horizontal cells in the mammalian retina.

We have used the neurofibrillar method of Gros-Schultze to stain the axonless horizontal cells of capybara, agouti, cat, and rabbit retinae. In all of these species, we have found two unusual horizontal cell morphologies: displaced horizontal cells and biplexiform horizontal cells. The displaced horizontal cells have perikarya located in the ganglion cell layer and dendrites branching in the inner plexiform layer. Many dendrites take an ascending trajectory to branch in the outer plexiform layer. The biplexiform horizontal cells are normally placed horizontal cells with descending processes that branch in the inner plexiform layer. Both cell types occur mainly in the retinal periphery, near the ora serrata. They are more numerous in the capybara retina, where they represent as much as 50% of the axonless horizontal cells of the retinal periphery.

Animals↗
PubMed2002

Suppression by zinc of AMPA receptor-mediated synaptic transmission in the retina.

Zinc is strikingly co-localized with glutamate-containing vesicles in the synaptic terminals of retinal photoreceptors, and it is thought to be co-released with glutamate onto postsynaptic neurons such as horizontal cells and bipolar cells. Here we examined exogenous zinc modulation of glutamate receptors on cultured retinal horizontal cells using patch-clamp recording and endogenous zinc effect on intact horizontal cells using intracellular recording techniques. Application of 3, 30, and 300 microM zinc reduced the whole cell peak current of response to 200 microM glutamate by 2, 30, and 56%, respectively. Zinc suppression of glutamate response persisted in the presence of 10 microM cyclothiazide (CTZ). Glutamate responses of outside-out patches were completely abolished by 30 microM 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), and the receptor desensitization was blocked by 30 microM CTZ, indicating that receptor target for the zinc action on horizontal cells is alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA) receptors. Zinc decreased the amplitude of outside-out patch peak current without an effect on either its 10-90% rise time or the rate of receptor desensitization. Dose-response curves for glutamate show that zinc reduced the maximal current evoked by glutamate and increased EC(50) from 50 +/- 3 to 70 +/- 6 microM without changing the Hill coefficient. Chelation of endogenous zinc with 1 mM Ca-EDTA depolarized horizontal cells in the intact retina by 3 mV, consistent with relief of the partial glutamate receptor inhibition by zinc. Overall, the results describe a unimodal form of zinc modulation of AMPA-type glutamate receptor responses not previously described in native neuronal preparations and a novel role for endogenous zinc in modulating neurotransmission.

Animals↗
PubMed1988

GABA release from Xenopus retina does not correlate with horizontal cell membrane potential.

The relationship between horizontal cell membrane potential and the release of GABA was explored in the retina of Xenopus laevis. The intracellularly recorded membrane potential of horizontal cells was monitored while the retina was exposed to different concentrations of depolarizing agents. The dose-response curves obtained revealed a rise from 5 to 95% maximum depolarization in 0.5-1.5 log unit concentration change. The molar concentrations that elicited a 20 mV depolarization were 40 mM (potassium), 0.8 mM (glutamate), 0.8 mM (glycine), 5 microM (kainate) and 1.3 microM (quisqualate). Autoradiography revealed that radiolabel was accumulated almost exclusively by horizontal cells when isolated retinas were incubated in medium containing 1 microM [3H]GABA. Thus, retinal release of radioactivity was used as a measure of [3H]GABA release from horizontal cells. Endogenous GABA released from retinas was measured using high performance liquid chromatography and was taken to reflect both amacrine and horizontal cell GABA pools. The release of both [3H]GABA and endogenous GABA was stimulated by glutamate, kainate and potassium, but not by glycine or quisqualate. Similar dose-response curves for GABA release and for depolarization were obtained in the case of potassium and kainate but not for glutamate. Potassium-evoked release either of endogenous GABA or [3H]GABA was both calcium- and sodium-dependent, whereas kainate- or glutamate-evoked GABA release was sodium-dependent but calcium-independent. The results indicate that depolarization per se is not necessarily associated with transmitter release in Xenopus retinal horizontal cells. It is suggested that the action of a given neurotransmitter upon the efflux of GABA from horizontal cells may depend on the degree to which it modifies the sodium conductance of the horizontal cell.

Animals↗
PubMed1997

Both high- and low voltage-activated calcium currents contribute to the light-evoked responses of luminosity horizontal cells in the Xenopus retina.

We examined the contribution of two intrinsic voltage-dependent calcium channels to the light-evoked responses of a non-spiking retinal neuron, the horizontal cell (HC). HC's isolated from the Xenopus retina were studied by the whole cell version of the patch clamp. In a mixture of agents which suppressed Na- and K-dependent currents, we identified a transient, low voltage-activated Ca current suppressed by Ba2+ and blocked by Ni2+ (T-type) and a sustained, high voltage-activated, dihydropyridine-sensitive Ca current that was enhanced by Ba2+ (L-type). We made simultaneous intracellular recordings from rods and HC's in the intact, dark-adapted Xenopus retina. Under certain stimulus conditions, transient oscillations appeared in HC responses but were absent in rod light-evoked waveforms. One type of transient was seen at relatively hyperpolarized potentials (< -45 mV), was enhanced by Sr2+ and inhibited by Ni2+. It thus appears to depend on a T-type Ca-current. A second type of oscillation was seen to be superimposed on a prolonged depolarizing wave following light off in the HC and as spike-like depolarizations in rods. These oscillations were enhanced by Ba2+ and Sr2+, but blocked by the dihydropyridine, nifedipine, indicating their dependence on an L-type calcium conductance. All calcium-dependent oscillations were suppressed by 0.05-0.5 mM Co2+. Suppression of glutamate neurotransmission with CNQX or kynurenate, or glycine neurotransmission with strychnine, enhanced the HC oscillations.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Slow light and dark adaptation of horizontal cells in the Xenopus retina: a role for endogenous dopamine.

A role for endogenous dopamine in the control of rod and cone contributions to a second-order retinal neuron, the horizontal cell (HC) was studied in the Xenopus retina. Relative rod and cone contributions were estimated from HC responses to scotopically balanced 491- and 650-nm flashes. In eyecups prepared in light then placed in darkness, cone input to the HC slowed and diminished on a time scale of hours. The decline in cone input was balanced by a slow growth of rod input to the HC. Administration of D-amphetamine, a dopamine releasing agent, restored the light-adapted waveform. The kinetics of slow light adaptation were examined by recording HC responses from eyecups that had been dark-adapted previously for 11-14 h. When test flashes fell on a dark field, cone input to the HC grew for 2-4 h, reached a plateau, and later declined. If, however, flashes were superimposed on a weak background field, cone input to the HC continued to increase monotonically at about 10%/h. This increase was abolished by superfusion with a nonspecific dopamine receptor blocker, cis-flupenthixol (50 microM), resulting in the complete suppression of cone-to-horizontal cell synaptic transfer and the enhancement of rod-to-horizontal cell communication. Subcutaneous injection of reserpine, a drug that depletes dopamine stores (2 mg/kg on 1-4 successive days), or intraocular injection of the dopamine neurotoxin, 6-hydroxydopamine (10-30 micrograms) slowed and reduced the amplitude of cone input to the HC, even in completely light-adapted eyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Calbindin-D 28 kD and parvalbumin in the horizontal cells of rat retina during development.

PURPOSE: Calbindin-D 28K (CaD) and parvalbumin (PV) are calcium-binding proteins thought to act as an intraneural calcium ion buffering system in the central nervous system. We previously reported that PV appears at birth in some cells in the outer portion of the nuclear layer of the retina that can differentiate into horizontal cells. CaD is also distributed in horizontal cells; however, it is not clear at which developmental stage CaD appears. METHODS: The development of horizontal cells and the distribution of CaD and PV was examined ultrastructurally and immunohistochemically in rat retinas from birth (P0) to postnatal day 50 (P50). RESULTS: Our ultrastructural data showed clear differentiation of horizontal cells from other retinal cells in the early postnatal days. These cells became nearly mature around P10 to P12. PV appeared in the outer nuclear layer at birth (P0) and, by P7, was observed in the ganglion cell layer, amacrine cells, and horizontal cells. CaD-immunoreactive cells, however, were not seen in any portions of the retina until P7. At P10, CaD-immunoreactivity was faintly observed in horizontal cells, and its immunoreactivity gradually increased in the horizontal cells from P10 to P15 when the eyes of the rats opened. CaD was not found in the ganglion cell layer or in amacrine cells at any period examined. CONCLUSION: In the horizontal cells, PV appeared when they were ultrastructurally distinguished from other retinal cells, while CaD appeared when they already had some structure for endocytosis and synaptic transmission, suggesting that PV and CaD may be good morphological and functional markers for horizontal cells, respectively.

Animals↗
PubMed1987

Joro spider venom: glutamate agonist and antagonist on the rod retina of the dogfish.

The venom of the Joro spider, reported to block glutamate action selectively at some glutaminergic synapses, was applied focally to rod horizontal and on-bipolar cells in dark-adapted retinal slices. The venom hyperpolarized horizontal cells in the dark and blocked their responses to light. Depolarization of horizontal cells by ionophoretic pulses of L-glutamate, L-aspartate or kainate was antagonized by the toxin in a slowly reversible manner. These results are consistent with other evidence for glutamate as the rod neurotransmitter acting on a single postsynaptic receptor type on horizontal cells. In contrast, the venom, like glutamate, closed the same ion channels of on-bipolar cells as the transmitter, thereby blocking light responses of on-bipolars. Joro spider toxin distinguishes the glutamate receptor-channel complexes of rod horizontal and on-bipolar cells.

Animals↗
PubMed1995

Expression of neurofilament proteins by horizontal cells in the rabbit retina varies with retinal location.

Classical neurofibrillar staining methods and immunocytochemistry with antibodies to the light, medium and heavy chain subunits of the neurofilament triplet have been used for in situ and in vitro investigation of the organization of neurofilaments in A- and B-type horizontal cells of the adult rabbit retina. Surprisingly, their expression and organization within a cell is dependent on its location along the dorso-ventral axis of the retina. A-type horizontal cells in superior retina consistently stained with a wide variety of neurofibrillar methods to reveal neurofibrillar bundles, which immunocytochemistry showed to contain all three neurofilament subunits. A-type horizontal cells in inferior retina were uniformly refractory to neurofibrillar staining, although they expressed all three subunits. However, there was less of the light and medium subunits; the organization of the filaments into bundles (neurofibrils) is minimal. B-type horizontal cells could not be stained with any neurofibrillar method and were not recognizable by in situ immunocytochemistry. However, B-type cells could be seen to express all three subunits in vitro, but the expression of the light and medium subunits was weak. There was only a slight difference between B-type cells taken from superior and inferior retina. Combined with the results of recent transfection studies, these findings suggest that the amount of the light neurofilament subunit present in a horizontal cell determines its content of neurofibrillar bundles, and that rabbit horizontal cells may contain more neurofilament protein, particularly of the heavy subunit, than is used for neurofilament formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Retinal neurotransmitter interaction as reflected in horizontal cell spatial behaviour.

The effects of 5-hydroxytryptamine (5-HT) and its precursors 5-hydroxytryptophan (5-HTP) and L-tryptophan (L-Tryp) on the spatial properties of horizontal cells were studied in the isolated and perfused retina of the teleost Eugerres plumieri. All three compounds produce a contraction of the receptive field, evaluated by the ratio of responses evoked by local and distant light stimuli. This is the result of cell uncoupling, revealed by the hindrance to diffusion of intracellularly injected Lucifer yellow. Similar effects are produced by dopamine (DA) and the effectiveness is DA much greater than 5-HT greater than 5-HTP greater than L-Tryp. All these effects are blocked by Haloperidol. HPLC studies of endogenous DA release reveal that it occurs when isolated retinas are incubated with 50 mM potassium, 10 microM 5-HT or 5-HTP, but is not found with up to 1 mM L-Tryp. The results indicate that indolaminergic cells induce the release of DA from interplexiform cells, which in turn uncouples horizontal cells in the fish retina.

5-Hydroxytryptophan↗
PubMed1991

Feedforward lateral inhibition in retinal bipolar cells: input-output relation of the horizontal cell-depolarizing bipolar cell synapse.

Lateral inhibition is the ubiquitous strategy used by visual neurons for spatial resolution throughout the animal kingdom. It has been a puzzle whether lateral inputs in retinal bipolar cells are mediated by the horizontal cell (HC)-cone feedback synapse, by the HC-bipolar cell feedforward synapse, or by both. By blocking the central inputs of the depolarizing bipolar cells (DBCs) with L-2-amino-4-phosphonobutyrate, we were able to eliminate the contribution of the feedback synapse and to demonstrate the postsynaptic light response in DBCs mediated by the HC-DBC feedforward synapse. The HC-DBC feedforward synapse contributes roughly one-third of the surround response whereas the HC-cone-DBC feedback synapse probably contributes the rest.

Ambystoma↗
PubMed1989

Neurotransmission in the frog retina: possible physiological and histological correlations.

In the frog retina, extracellular recordings of transient ganglion cells have shown that the inhibitory surround of the receptive field of these cells was mediated by gamma-aminobutyric acid and acetylcholine (through the nicotinic receptors). Histoautoradiographic and immunocytochemical studies for the two respectively have shown that these neurotransmitters can act through horizontal and amacrine cells. The separation of the ON and OFF channels mediated by glutamate at the bipolar cell level may also be obtained by glycine and/or acetylcholine (through muscarinic receptors). Respective histoautoradiographic and immunocytochemical studies indicate that these neurotransmitters act at the amacrine cell level. These data are consistent with the functional separation of spatial and temporal organization of retinal information, with horizontal cells especially responsible for the spatial organization of the ganglion cell responses and amacrine cells involved in both spatial and temporal organization of the responses.

Acetylcholine↗