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PubMed1983

Morphologic changes in teleost primary and secondary retinal cells following brief exposure to light.

Light adaptive morphologic changes in the teleost retina, such as movements of rods, cones, and epithelial pigment and spinule formation on horizontal cell terminals, are normally associated with continual exposure to light. Depending on a variety of factors these processes are generally completed within 30-60 min. In this report we show that a brief exposure to light (1-2 min) preceded and followed by darkness is sufficient to elicit these changes in four species of teleost; the trout (Salmo gairdneri), the tench (Tinca tinca), the carp (Cyprinus carpio), and the goldfish (Carassius auratus). A brief pulse is as effective in causing cone migration and an increase in the number of spinules as continual exposure; however, it is sometimes less effective in causing pigment migration. The photomechanical changes following a brief period of light are always completed more quickly and show greater species variability than the formation of spinules. These results show that the various morphologic manifestations of light adaptation are autonomous processes that need only a short pulse of light to trigger the whole sequence of events. This is of interest when considering their control mechanisms and may have consequences for physiologic work involving experiments on dark-adapted eyes.

Adaptation, Physiological↗

PubMedDate not supplied

The ipsilateral retinal projection in the fat-tailed dunnart, Sminthopsis crassicaudata.

The population of retinal ganglion cells which project ipsilaterally in the brain was examined in the fat-tailed dunnart, Sminthopsis crassicaudata, following injection of horseradish peroxidase into one optic tract. Retinae were examined as wholemounts and optic nerves as serial sections. In addition, visual fields were measured ophthalmoscopically. Ipsilaterally projecting ganglion cells were located temporal to a line which ran vertically through the middle of the area centralis and extended medially to define a ventrolateral crescent. Temporal to the naso-temporal division, a mean of 77% of ganglion cells projected ipsilaterally; these cells represented 20% of the total ganglion cell population. The magnitude and retinal location of the ipsilateral projection correlated with the extensive binocular field which measured 180 deg in the vertical (from 20 deg below the horizontal axis to 70 deg beyond the zenith) and 140 deg in horizontal meridian. Ipsilaterally projecting axons were restricted to the lateral third of the optic nerve along its length, sharing territory with contralaterally projecting axons.

Animals↗

PubMed1986

Spatiotemporal organization of the receptive fields of retinal ganglion cells in the cat: a phenomenological model.

The reorganization of ganglion cell receptive fields (RFs) with different levels of light adaptation was investigated by means of spontaneous contour planes (SCPs). The SCP shows the spatiotemporal characteristics of the cell responses to a small bar of light switched on and off at 31 separate points along the RF horizontal axis. We assume a radial symmetry of RFs. A mathematical function describing the SCPs and their light level induced changes was found. Its form suggests that three mechanisms (central, surround and phasic) are required to account for RF organization of both homogeneous and heterogeneous retinal ganglion cells. The phasic component is probably identical with the nonlinear mechanism described by other authors. Responses to moving stimuli .were also investigated and correlated with the spatiotemporal organization of the RF.

Animals↗

PubMed1989

B-wave of the electroretinogram. A reflection of ON bipolar cell activity.

Light-evoked intraretinal field potentials (electroretinogram, ERG) have been measured simultaneously with extracellular potassium fluxes in the amphibian retina. The application of highly selective pharmacologic agents permitted us to functionally isolate various classes of retinal neurons. It was found that: (a) application of APB (2-amino-4-phosphonobutyrate), which has previously been shown to selectively abolish the light responsiveness of ON bipolar cells, causes a concomitant loss of the ERG b-wave and ON potassium flux. (b) Conversely, PDA (cis 2,3-piperidine-dicarboxylic acid) or KYN (kynurenic acid), which have been reported to suppress the light responses of OFF bipolar, horizontal, and third-order retinal neurons, causes a loss of the ERG d-wave as well as OFF potassium fluxes. The b-wave and ON potassium fluxes, however, remain undiminished. (c) NMA (N-methyl-DL-aspartate) or GLY (glycine), which have been reported to suppress the responses of third-order neurons, do not diminish the b- or d-waves, nor the potassium fluxes at ON or OFF. This leads to the conclusion that the b-wave of the ERG is a result of the light-evoked depolarization of the ON bipolar neurons. This experimental approach has resulted in two further conclusions: (a) that the d-wave is an expression of OFF bipolar and/or horizontal cell depolarization at the termination of illumination and (b) that light-induced increases in extracellular potassium concentration in both the inner (proximal) and outer (distal) retina are the result of ON bipolar cell depolarization.

Ambystoma↗

PubMed1996

Retinal neurons of the California ground squirrel, Spermophilus beecheyi: a Golgi study.

Although the optic nerve fibers of the cone-dominant ground squirrel retina have been well studied physiologically, the morphological details of the retinal neurons have not. To that end, retinal neurons of the California ground squirrel have been studied in Golgi-impregnated wholemounts. Two types of horizontal cell have been identified: H1 has an axon and axon terminal, whereas H2 is axonless. The dendritic field of H1 cells enlarges in a nonuniform manner with increasing displacement from the central retina. The smallest examples lie centrally in the visual streak, and the largest occur in the superior periphery. Eight types of bipolar cell are distinguished by morphological differences in dendritic branching pattern and field size in the outer plexiform layer, cell body size, and layering within the inner nuclear layer and by the morphology and stratification of axon terminals in the inner plexiform layer. A large bistratified bipolar cell (B8) is introduced here; the other 7 types closely resemble those in the retinas of other sciurid species described by R.W. West (1976, J. Comp. Neurol. 168:355-378; 1978, Vision Res. 18:129-136). The B1 type is proposed as a blue cone bipolar cell. Amacrine cells are classified into 27 cell types. Six of these occur as mirror-image pairs across the inner plexiform layer, the soma of one of each pair being "displaced" to the ganglion cell layer. The best described of these pairs is the very elaborate starburst amacrine cell, A5, which stains regularly in these wholemounted retinas. Changes in dendritic field size of both A5 subtypes with retinal location are quantified. The morphology of three amacrine cell types identified in Spermophilus beecheyi suggests that their possible counterparts in S. mexicanus (West, 1976) were, as displaced amacrine cells, misidentified as ganglion cells. Amacrine cell types that may play roles in the rod pathway, the blue cone pathway, and ganglion cell directional selectivity are discussed. No type of interplexiform cell was observed. Ganglion cells are classified into 19 cell types, 9 of which probably correspond to the ganglion cells described by West (1976) in the Mexican ground squirrel. The bistratified G11 cell is proposed as an ON-OFF directionally selective type.

Animals↗

PubMed2004

Requirement of multiple basic helix-loop-helix genes for retinal neuronal subtype specification.

Retinal precursor cells give rise to six types of neurons and one type of glial cell during development, and this process is controlled by multiple basic helix-loop-helix (bHLH) genes. However, the precise mechanism for specification of retinal neuronal subtypes, particularly horizontal neurons and photoreceptors, remains to be determined. Here, we examined retinas with three different combinations of triple bHLH gene mutations. In retinas lacking the bHLH genes Ngn2, Math3, and NeuroD, horizontal neurons as well as other neurons such as bipolar cells were severely decreased in number. In the retina lacking the bHLH genes Mash1, Ngn2, and Math3, horizontal and other neurons were severely decreased, whereas ganglion cells were increased. In the retina lacking the bHLH genes Mash1, Math3, and NeuroD, photoreceptors were severely decreased, whereas ganglion cells were increased. In all cases, glial cells were increased. The increase and decrease of these cells were the result of cell fate changes and cell death and seem to be partly attributable to the remaining bHLH gene expression, which also changes because of triple bHLH gene mutations. These results indicate that multiple bHLH genes cross-regulate each other, cooperatively specify neuronal subtypes, and regulate neuronal survival in the developing retina.

Animals↗

PubMed1985

Retinal changes in the selenium deficient rat.

The retina of rats with selenium deficiency was studied by light and electron microscopy. Nuclei of the inner nuclear layer were decreased in number after 12 months following selenium deficient diet feeding, although photoreceptor nuclei were kept normal in number. Nuclei of amacrine and horizontal cells were prominently decreased. More than 1.5 years after feeding selenium deficient diet, the retina showed prominent decrease of photoreceptor cells, but no increase of lipofuscin granules in the retinal pigment epithelium. In conclusion, selenium deficiency induces some kind of nerve damage.

Animals↗

PubMed1981

Retinal amacrine cell involvement in Tay-Sachs disease.

Ultrastructural study of the retina from a patient with Tay-Sachs disease disclosed that amacrine cells as well as ganglion cells were loaded with numerous membranous cytoplasmic bodies, suggesting an accumulation of GM2 ganglioside, whereas the horizontal cells, bipolar cells, and photoreceptor cells were intact. Chromatography of lipids from the retina showed a prominent spot of GM2 ganglioside. These facts suggest that lipid metabolism in amacrine cells may be different from that in other retinal cells.

Child, Preschool↗

PubMed2005

Distinct patterns of expression of the RB gene family in mouse and human retina.

Although RB1 function is disrupted in the majority of human cancers, an undefined cell of developing human retina is uniquely sensitive to cancer induction when the RB1 tumor suppressor gene is lost. Murine retinoblastoma is initiated only when two of the RB family of genes, RB1 and p107 or p130, are inactivated. Although whole embryonic retina shows RB family gene expression by several techniques, when E14 developing retina was depleted of the earliest differentiating cells, ganglion cells, the remaining proliferating murine embryonic retinal progenitor cells clearly did not express RB1 or p130, while the longer splice form of p107 was expressed. Each retinal cell type expressed some member of the RB family at some stage of differentiation. Rod photoreceptors stained for the RB1 protein product, pRB, and p107 in only a brief window of postnatal murine development, with no detectable staining for any of the RB family proteins in adult human and mouse rod photoreceptors. Adult mouse and human Muller glia, ganglion and rare horizontal cells, and adult human, but not adult mouse, cone photoreceptors stained for pRB. The RB gene family is dynamically and variably expressed through retinal development in specific retinal cells.

Animals↗

PubMed1996

Models of ganglion cell topography in the retina of macaque monkeys and their application to sensory cortical scaling.

We devised mathematical models of the topography of ganglion cells in the retina of macaque monkeys. The models consisted of a sum-of-three exponentials function fitted to measurements of ganglion cell density made on the nasal horizontal meridian, combined with known anisotropies across the horizontal and vertical meridians by means of elliptic interpolation to provide a full description of their density across the whole of the retinal surface. Integration using standard numerical techniques allowed the number of ganglion cells in arbitrary regions of the retina to be estimated. The topography of actual and effective total ganglion cell populations, and of primate alpha and gamma retinal ganglion cells, was modelled on previously published data. The models were used to test the hypothesis that the retinal projection to the striate cortex in macaque monkeys is peripherally scaled (i.e. merely reflects the eccentricity-dependent variation in density of ganglion cells in the retina) by comparing the cumulative proportion of ganglion cells with the cumulative proportion of cortical area as a function of eccentricity in the visual field. Discrepancies between the two curves indicated that the fovea and immediately surrounding retina are overrepresented in the striate cortex (i.e. there is more cortex per ganglion cell in and near the fovea than in the periphery), and the fact that the discrepancies persisted out to 25-50 degrees of eccentricity showed that the overrepresentation cannot be explained by the lateral displacement of foveal ganglion cells.

Animals↗

PubMed2002

The influence of different retinal subcircuits on the nonlinearity of ganglion cell behavior.

Y-type retinal ganglion cells show a pronounced, nonlinear, frequency-doubling behavior in response to modulated sinewave gratings. This is not observed in X-type cells. The source of this spatial nonlinear summation is still under debate. We have designed a realistic biophysical model of the cat retina to test the influence of different retinal cell classes and subcircuits on the linearity of ganglion cell responses. The intraretinal connectivity consists of the fundamental feedforward pathway via bipolar cells, lateral horizontal cell connectivity, and two amacrine circuits. The wiring diagram of X- and Y-cells is identical apart from two aspects: (1) Y-cells have a wider receptive field and (2) they receive input from a nested amacrine circuit consisting of narrow- and wide-field amacrine cells. The model was tested with contrast-reversed gratings. First and second harmonic response components were determined to estimate the degree of nonlinearity. By means of circuit dissection, we found that a high degree of the Y-cell nonlinear behavior arises from the spatial integration of temporal photoreceptor nonlinearities. Furthermore, we found a weaker and less uniform influence of the nested amacrine circuit. Different sources of nonlinearities interact in a multiplicative manner, and the influence of the amacrine circuit is approximately 25% weaker than that of the photoreceptor. The model predicts that significant nonlinearities occur already at the level of horizontal cell responses. Pharmacological inactivation of the amacrine circuit is expected to exert a milder effect in reducing ganglion cell nonlinearity.

Amacrine Cells↗

PubMed1999

Evidence of metabotropic glutamate receptor subtypes found on catfish horizontal and bipolar retinal neurons.

We have used electrophysiological, pharmacological and immunological techniques to determine which classes of metabotropic glutamate receptors exist on cone horizontal cells in the catfish retina. Patch-clamp recordings in acutely dissociated cone horizontal cells provide evidence that group I and III metabotropic glutamate receptors exist, and are linked to modulation of a voltage-gated calcium current. Group II metabotropic glutamate receptor agonists did not affect the calcium current. Immunocytochemical techniques were used to study the localization of metabotropic glutamate receptor subtypes found in the catfish retina. Antibodies raised against group I (metabotropic glutamate receptor 1alpha, metabotropic glutamate receptor 5), group II (metabotropic glutamate receptor 2/3) and group III (metabotropic glutamate receptor 6) metabotropic glutamate receptor subtypes were used to label acutely dissociated horizontal, bipolar and Müller cells. Results from immunostaining provide evidence that cone horizontal cells express group I (metabotropic glutamate receptor 1alpha, metabotropic glutamate receptor 5) and group III (metabotropic glutamate receptor 6), but not group II (metabotropic glutamate receptor 2/3) receptor subtypes, consistent with our electrophysiological results. Cone horizontal cells exposed to anti-metabotropic glutamate receptor 1alpha, 5 or 6 antibodies all demonstrated diffuse overall staining, with patches of dark immunostaining found on both dendritic processes and cell somata. In catfish bipolar cells, all four of the anti-metabotropic glutamate receptor antibodies stained the processes and cell bodies of bipolar cells homogeneously. There was no evidence for a group of bipolar cells that did not stain with the antimetabotropic glutamate receptor antibodies, although the densest immunostaining occurred when bipolar cells were incubated with the anti-metabotropic glutamate receptor 6 antibody. Müller cells did not show immunostaining against any anti-metabotropic glutamate receptor antibody. Our non-immune controls confirmed that immunostaining was specific for the antigen, and immunoblots were performed to demonstrate the specificity of the antibodies in catfish retina. These results support the hypothesis that group I and III metabotropic glutamate receptor subtypes are found on catfish horizontal cells, and group I, II and III metabotropic glutamate receptor subtypes are expressed on catfish bipolar cells. The metabotropic glutamate receptors on catfish cone horizontal cells act to modulate the voltage-gated sustained calcium current found on these cells.

Animals↗

PubMed1983

An excitatory amino acid antagonist blocks cone input to sign-conserving second-order retinal neurons.

cis-2,3-Piperidinedicarboxylic acid (PDA), an excitatory amino acid antagonist, reversibly blocked cone input to OFF bipolars and horizontal cells, whereas ON bipolars were relatively unaffected. Kainic acid effects were also blocked, indicating a postsynaptic mechanism of action. The use of PDA helps to characterize one of two classes of excitatory amino acid synaptic receptors that mediate cone influence in the outer retina.

Amino Acids↗

PubMed2006

Structural and functional consequences of trolox C treatment in the rat model of postnatal hyperoxia.

PURPOSE: Previous studies have shown that newborn rats exposed to hyperoxia within the first 2 weeks of life develop vasculopathy in addition to permanent changes in retinal structure and function. It has also been suggested that free radicals may be the source of these pathologic effects. Trolox C, a water-soluble analogue of vitamin E, was previously shown to limit the vascular consequences of exposure to postnatal hyperoxia. The aim of this study was to investigate whether trolox C could also help prevent the functional (electroretinography) and structural (retinal histology) consequences associated with oxygen-induced retinopathy (OIR). METHODS: Newborn albino Sprague-Dawley rats exposed or not exposed to hyperoxia received daily injections of trolox C in doses of 300, 600, and 900 microg/kg (total volume, 50 microL). The effect of treatment was evaluated through electroretinography and retinal histology. RESULTS: Although trolox C tended to have a retinoactive effect on the normal retina, normalization of the hyperoxia-treated group to hyperoxic control and of the normoxia-treated group to normoxic control revealed that the a-wave remained relatively unaffected by hyperoxia exposure and by treatment with trolox C, the efficacy of trolox C at doses of 600 and 900 microg/kg largely outweighed the retinoactive effect, and the oscillatory potentials (OPs) benefited to the greatest extent from trolox C treatment. Furthermore, trolox C was able to limit the reduction in outer plexiform layer thickness but not the concomitant reduction of the horizontal cell count, each of which is associated with OIR. CONCLUSIONS: These results show that, as had been previously demonstrated with retinal vasculature, trolox C limited the retinal functional and structural damages inherent in the rat model of OIR. However, despite treatment, there were still signs (albeit less severe) indicative of OIR. This suggests, as previously advanced, that the pathophysiology of OIR is not solely caused by the action of free radicals or that trolox C is inadequate in treating all aspects of OIR.

Animals↗

PubMed1986

Discharges of neurons in the dorsal paraflocculus of monkeys during eye movements and visual stimulation.

Extracellular recordings were obtained from 319 input units and 304 Purkinje cells (P-cells) in the dorsal paraflocculus of alert monkeys trained to fixate a visual target. They changed discharge rates with either eye movement, eye position, or visual stimulus movement. Of the 319 input units, recorded in the granular layer or white matter, most were mossy fibers (MFs), but 90 (28%) showed characteristic cellular spikes. The latter units were probably granular cells (p-GC). Of the 319 input units, 163 (51%) showed bursts with saccades (burst units) and 62 (19%) showed a prelude on the average 124 ms prior to the onset of saccade (long-lead burst units). Sixty-five (20%) had tonic activity related to eye position and also showed bursts with saccades (burst-tonic units), and the remaining 29 (9%) showed only tonic activity (tonic units). MFs and p-GCs showed no significant differences in the proportion of each type of unit or in their response properties. The majority of burst units (63%) were pan directional, whereas all long-lead burst units had directional selectivity. The preferred directions of long-lead burst, burst tonic, and directionally selective burst units were found in all four quadrants. Position-related activity was found in 48% of the burst-tonic and tonic units to be linearly related to eye position and to show position threshold. The other units also had position thresholds but their activity was not monotonically related to fixation position. Six climbing fibers (CFs), 32 input units (including 13 p-GC), and 8 P-cells showed cyclic responses during sinusoidal movements of a visual pattern. One class of MF units (57%) responded only to the direction, whereas the others responded to both the direction and retinal-slip velocity. Both CF and P-cell units responded to sinusoidal retinal-slip velocity. Of 67 input units, 23 showed cyclic modulation in firing during sinusoidal eye movements in the horizontal plane. Nineteen were burst-tonic and four were tonic units. They also showed position sensitivity. The phase of the cyclic responses tended to lag behind the eye velocity during low-frequency trackings. Of 237 P-cells, 163 (68.8%) discharged with saccades (burst P-cells), 42 (17.7%) paused with saccades (pause P-cells), and 32 (13.5%) discharged with saccades in one direction and paused in the other (burst-pause P-cells). Position sensitivity was found in 38 P-cells; 12 were burst, 5 were pause, and 10 were burst-pause P-cells. Eleven did not respond with saccades.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1980

Retinal benzodiazepine receptors are destroyed by kainic acid lesions.

[3H]Diazepam binds to preparations of membranes from chicken retina. Two binding sites were detected; a high affinity site (KD, 1.8 nM and Bmax, 0.17 pmol/mg retina protein) and a low affinity site (KD, 132 nM and Bmax, 1.46 pmol/mg retinal protein). GABA stimulated [3H]diazepam binding to these retinal membranes. One week after injection of kainic acid into the eye, which destroys the horizontal and amacrine cells of the retina, the low affinity site disappeared, while the level of the high affinity site was hardly affected. These results establish that chicken retina contains benzodiazepine receptors, which are closely associated with GABA receptors. The benzodiazepine receptors are probably associated with horizontal and/or amacrine cell synapses which use GABA as a transmitter.

Animals↗

PubMedDate not supplied

Early appearance and transient expression of putative amino acid neurotransmitters and related molecules in the developing rabbit retina: an immunocytochemical study.

We have studied, by immunocytochemistry, the ontogeny of GABA, glycine, glutamate, glutamine, and taurine-containing cells in the rabbit retina. Amacrine cells show GABA immunoreactivity by embryonic day 25 (E25) and throughout postnatal life. By contrast, ganglion cells and horizontal cells are only transiently GABA-immunoreactive (-IR); few appear GABA-IR by the third postnatal week. At maturity, glycine is present in amacrine cells and in some bipolar cells. During development, putative ganglion cells transiently contained glycine between E25 and postnatal day 3 (P3), whereas immunolabelling in presumed amacrine cells and bipolar cells persists after birth. Ganglion cells, bipolar cells, photoreceptors, and some amacrine cells are glutamate-IR in the adult retina. Glutamate immunoreactivity first appears in the somata and processes of cytoblastic cells by E20 and is prominent by E25. Surprisingly, ganglion cells are not strongly glutamate-IR until just before eye-opening, at postnatal day 10 (P10), coincident with the appearance of glutamine in their somata and in Müller glial cells. Bipolar cells are glutamate-IR before they or Müller cells contain high levels of glutamine (at P10). Glutamate immunoreactivity in photoreceptors is progressively restricted to the inner segments by eye-opening. At no stage are presumed horizontal cells glutamate-IR or glutamine-IR, but some amacrine cells show glutamate- and glutamine-IR by P10. Taurine is localized to photoreceptors and Müller glial in the adult retina. Some cytoblasts are taurine-IR at E20; with ensuing development, taurine labelling becomes restricted primarily to Müller cells and photoreceptors; some putative bipolar cells may also be labelled. However, for a few days around birth, cells resembling horizontal cells, also show taurine immunoreactivity. The early appearance and often transient expression of these amino acids in retinal cells suggests that these neuroactive molecules may be involved in the structural and functional development of the retina.

Animals↗

PubMed1995

Identification and functional characterization of a dual GABA/taurine transporter in the bullfrog retinal pigment epithelium.

Intracellular microelectrodes, fluorescence imaging, and radiotracer flux techniques were used to investigate the physiological response of the retinal pigment epithelium (RPE) to the major retinal inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). GABA is released tonically in the dark by amphibian horizontal cells, but is not taken up by the nearby Müller cells. Addition of GABA to the apical bath produced voltage responses in the bullfrog RPE that were not blocked nor mimicked by any of the major GABA-receptor antagonists or agonists. Nipecotic acid, a substrate for GABA transport, inhibited the voltage effects of GABA. GABA and nipecotic acid also inhibited the voltage effects of taurine, suggesting that the previously characterized beta-alanine sensitive taurine carrier also takes up GABA. The voltage responses of GABA, taurine, nipecotic acid, and beta-alanine all showed first-order saturable kinetics with the following Km's: GABA (Km = 160 microM), beta-alanine (Km = 250 microM), nipecotic acid (Km = 420 microM), and taurine (Km = 850 microM). This low affinity GABA transporter is dependent on external Na, partially dependent on external Cl, and is stimulated in low [K]o, which approximates subretinal space [K]o during light onset. Apical GABA also produced a significant conductance increase at the basolateral membrane. These GABA-induced conductance changes were blocked by basal Ba2+, suggesting that GABA decreased basolateral membrane K conductance. In addition, the apical membrane Na/K ATPase was stimulated in the presence of GABA. A model for the interaction between the GABA transporter, the Na/K ATPase, and the basolateral membrane K conductance accounts for the electrical effects of GABA. Net apical-to-basal flux of [3H]-GABA was also observed in radioactive flux experiments. The present study shows that a high capacity GABA uptake mechanism with unique pharmacological properties is located at the RPE apical membrane and could play an important role in the removal of GABA from the subretinal space (SRS). This transporter could also coordinate the activities of GABA and taurine in the SRS after transitions between light and dark.

Animals↗