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PubMed1985

Distributions of aspartate aminotransferase and malate dehydrogenase activities in rat retinal layers.

Aspartate aminotransferase (AAT), an enzyme interconverting glutamate and aspartate, has been suggested to be a marker for glutamatergic and/or aspartatergic neurons. However, AAT, glutamate, and aspartate are also involved in cellular metabolism, e.g., the malate-aspartate shuttle. To investigate the extent to which AAT might be involved in these several functions in retina, the distribution of AAT activity in rat retinal layers was compared to that of malate dehydrogenase (MDH), an enzyme of aerobic metabolism proposed to be physically complexed with AAT in the malate-aspartate shuttle mechanism. The distribution of AAT activity in retinal layers closely paralleled that of MDH (correlation coefficient AAT versus MDH = 0.93). AAT activity was proportionately higher than MDH in the photoreceptor inner segments, containing a high density of mitochondria, and in the outer plexiform layer (OPL), containing photoreceptor terminals and bipolar and horizontal cell processes. The amount of total AAT activity in the inner segments related to the mitochondrial isoenzyme is almost twice that in the other layers tested, including the OPL. The correlation between AAT and MDH activities is consistent with AAT involvement in retinal energy metabolism, although other functions, such as neurotransmission, are possible.

Animals↗

PubMed2005

Human S-cone vision: relationship between perceptive field and ganglion cell dendritic field.

We measured the S-cone contrast threshold for stimuli of different size modulated along the white -90 deg direction in the isoluminant plane of DKL color space. The stimuli were presented at eccentricities of 5-30 deg in the horizontal temporal retinal meridian. Ricco's area of complete spatial summation was estimated using a bilinear fit of the log threshold/log area function. Ricco's area increased towards the retinal periphery to include an increasing number of S-cones while remaining 1.6-1.8 times larger than the dendritic field area of the small bistratified and parasol retinal ganglion cells. Assuming constant coverage factor by the dendritic field, Ricco's area incorporated a constant number (three to four) of small bistratified cells. It was also found that the threshold contrast for stimuli that matched Ricco's area was constant across the studied eccentricity range, similar to previous findings for achromatic vision. Our data support the point of view that this invariance is the result of a constant number of cells involved in stimulus detection.

Adult↗

PubMedDate not supplied

Ontogeny of preproenkephalin mRNA expression in the rat retina.

Endogenous opioid systems (i.e. opioid peptides and opioid receptors) modulate developmental events in the neonatal mammalian retina. In the present study, the mRNA encoding preproenkephalin A (PPE), the prohormone for the opioid growth factor (OGF), [Met5]-enkephalin, was studied in the developing and the adult retinas of rats. Northern analysis indicated the presence of a 1.4-kb message in the developing and adult retinas corresponding to rat PPE mRNA. Quantitation showed that PPE message was present on postnatal day 1 at 5% of the adult level, and increased during development until the adult quantity was reached by postnatal day 27. In situ hybridization experiments first detected the presence of PPE mRNA in retinal tissues during late gestation. In late prenatal and neonatal retinas, PPE message was associated with areas of the developing retina containing proliferating neuroblasts and postmitotic cells. Later in development, message appeared to be located primarily within the inner retina, with abundant PPE mRNA associated with putative horizontal cells of the inner nuclear layer (INL). The adult retina showed a similar pattern of PPE gene expression in the cells of the INL. These findings document that the gene expression in the retina for PPE begins in the fetus, continues during retinal development, and coincides with the presence of a PPE mRNA derivative ([Met5]-enkephalin) that regulates DNA synthesis during retinal ontogeny. Our results are also the first to show the presence of PPE message in the adult mammalian retina, suggesting transcription of an opioid gene in the mature visual system.

Animals↗

PubMed1984

Electronic simulation of ganglion cells of generalized vertebrate cone retina.

Electronic simulation of generalized vertebrate cone retina consists of 43 X 41 grid of red-, green-, and blue-sensitive cones. Each retinal element is simulated by a linear summator in series with a leaky integrator and spatial-temporal properties are developed by spatial organization of cone mosaic into unit hexagons and interplay of antagonistic inputs of differing time courses. Model has full compliments of horizontal and bipolar cells including color- and non-color coding as well as single- and double-opponent receptive fields for bipolar cells. Electronic simulation also has negative feedback from L-horizontal cells to cones. Ganglion cells are formed by convergence of 7 bipolar cells, either all same and thus homogeneous, or else with a central-DPBC (or HPBC) and 6 surround-HPBCs (or DPBCs) and thus non-homogeneous. Responses of color- and non-color-coded ganglion cells as well as single- and double-opponents are investigated with stationary and moving light spots using white and colored lights. While responses to stationary light spots are predictable from digital models, responses to moving spots are complicated by differing time lags of components involved in total response. Therefore, responses to moving stimuli are more readily simulated by analogue models.

Animals↗

PubMed1994

The retinal dopamine network alters the adaptational properties of retinal ganglion cells in the cat.

1. Single-unit extracellular recordings of optic tract fibers were used to study ganglion cell (GC) response properties of the intact cat eye before and after the intravitreal injection of haloperidol or SCH23390, dopamine-specific antagonists. Nearly all of the dopaminergic cells in the cat retina are amacrine cells (ACs); thus the dopamine antagonists are thought to primarily block the postsynaptic effects of these dopaminergic amacrine cells. All GCs encountered were subjected to a battery of receptive-field (RF) tests, including classification as X or Y, and as ON or OFF. 2. The effects of haloperidol were greatest in the light-adapted OFF-center pathways and especially in the OFF-center Y-cell. Within 30 min of haloperidol injection, both the spontaneous and light-evoked activity of the OFF-center Y-cell fell to zero, but when the same cell was exposed to lower levels of steady-state background illumination (scotopic levels), the response of the cell once again became robust. 3. OFF-Center Y-cells that had partially recovered from the drug effects and OFF-center X-cells recorded when the drug effect was maximal both possessed intensity-response curves that were shifted to the right of normal. 4. Recovery from the drug effects reflect supranormal responses after the initial response reductions and may be due to haloperidol's action on the dopamine autoreceptor. 5. Of the ON-center cells, only the Y-cells showed response alterations; possessing higher spontaneous activities and slightly reduced amplitudes to RF center (RFC) illumination. 6. The effects of SCH23390 paralleled those of haloperidol except that the onset was faster and the duration of the action of SCH23390 was much shorter, and no supranormal responses followed the initial effects. 7. Dark-adaptation functions of OFF-center GCs revealed a normal rod-cone shift; however, SCH23390 eliminated the rod-cone break, and threshold quickly fell to that of the rod mechanism. 8. The dopaminergic neurons of the cat retina appear to play an important role in regulating the activity of retinal OFF-center pathways in the photopically adapted eye, and one of its functions may be to control the relative contributions of the rod and cone systems to the response properties of light-adapted OFF-center GCs. 9. It is argued that dopamine is released in the light and enhances cone pathway activity, perhaps in the outer retina at bipolar and horizontal cells, and suppresses rod pathway activity, perhaps in the inner retina at amacrine cells.

Adaptation, Ocular↗

PubMed1998

Developmental study of Müller cells in the rat retina using a new monoclonal antibody, RT10F7.

We produced the monoclonal antibody RT10F7, characterized its antigenic specificity and expression in the adult and developing retina, in cultured retinal cells and in other parts of the central nervous system. In metabolically-labelled retinal cultures RT10F7 immunoprecipitated a protein of approximately 36,000 mol. wt. In the adult, RT10F7 stained endfeet of Müller cells in the ganglion cell layer, four horizontal bands in the inner plexiform layer, and radial fibres in the outer plexiform layer which terminated at the outer limiting membrane. In the inner nuclear layer, most somata were underlined by Müller processes that wrapped around them, but some cell bodies were immunoreactive for RT10F7 in the cytoplasm. During development, postnatal day 21 was the first age at which the adult pattern of immunoreactivity was present, although a fourth band in the inner plexiform layer was less clear than for the adult. By 14 and eight days after birth, the pattern of RT10F7 immunoreactivity approximated that of the adult; however, only three bands and one band were present, respectively, in the inner plexiform layer. At earlier ages, postnatal days 4, 1 and embryonic ages 19 and 15, the monoclonal antibody stained Müller cell endfeet and radial fibres, from the inner plexiform layer through the neuroblastic layer to the outer limiting membrane. At these ages, the immunoreactivity was more prominent at the level of Müller cell endfeet. The monoclonal antibody stained glia in preparations of dissociated retinal cells maintained in culture but not astrocytes or oligodendrocytes from optic nerve cultures. In brain sections, tanycytes exhibited RT10F7 immunoreactivity. The monoclonal antibody RT10F7 recognized a specific cell type in the retina, the Müller cell. In the adult and developing retina, RT10F7 recognized an antigen that is present primarily in Müller cell processes. This feature allowed us to follow the maturation of the Müller cell and correlate it with developmental events in the retina. RT10F7 is a specific marker for Müller cells in vivo and in vitro and may be useful for studies of function of Müller cells after ablation or after injuries that are known to activate Müller cells.

Animals↗

PubMed1977

Growth of the adult goldfish eye. III. Source of the new retinal cells.

The manner in which new cells are added to the growing adult goldfish retina was examined using 3H-thymidine radioautography. Cell proliferation leading to the formation of neurons is restricted to the retinal margin at the ora terminalis. New retina is added in concentric rings, with slightly more growth dorsonasally. The rate of cell addition is variable, averaging 12,000 cells/day. These new cells account for about 20% of the total increase in retinal area; the remaining 80% is due to hypertrophy, or expansion, of the retina. In contrast to all of the other retinal cells, the rods do not appear to participate in the retinal expansion. This hypothesized immobility of the rods would create a shearing strain between the retinal layers resulting in a shift in their position relative to the other cells. Were they to maintain synaptic contacts with the same horizontal and bipolar cells, the rod axons would have to be elongated peripherally or the post-synaptic cell dendrites displaced centrally. Since neurons with this morphology have not been found in the goldfish retina, these observations suggest that the rods must be changing their synaptic connections as the retina grows.

Animals↗

PubMed1985

White perch horizontal cells in culture: methods, morphology and process growth.

Four types of horizontal cells are recognized in primary cultures of the adult white perch retina. Immediately after isolation, all horizontal cell types show fine terminal processes. However, these fine processes disappear over the next 12-24 h and the cells typically round up partially. After 2-4 days in culture, new processes appear on the horizontal cells, and these usually grow substantially with time. By 14-21 days, processes several hundred micrometers in length are observed in the retinal culture dishes. Processes from different cells intertwine and contacts that appear synaptic in nature are observed.

Animals↗

PubMed1987

N-acetylaspartylglutamate immunoreactivity in neurons of the cat's visual system.

The acidic dipeptide, N-acetylaspartylglutamate (NAAG) was identified immunohistochemically within neurons of the cat's visual system. In the retina, NAAG-like immunoreactivity was observed in some horizontal and amacrine cells at the inner and outer margins of the bipolar cell layer. NAAG-like immunoreactivity was also observed in many retinal ganglion cell bodies, their neurites, and the neuropil of their target areas, the lateral geniculate nucleus (LGN) and the superior colliculus. Additionally, peptide immunoreactivity was also seen in the projection neurons of the LGN, in cells of the pulvinar nucleus, and in the pyramidal cells of layers III and V in areas 17, 18 and 19 of the cerebral cortex. These data suggest that NAAG or a structurally related molecule may have a prominent role in the communication of visual signals at retinal, thalamic and cortical levels.

Animals↗

PubMed1994

Nitric oxide synthase in the CNS of the Atlantic salmon.

This study describes for the first time the presence and distribution of the nitric oxide (NO) synthesizing enzyme, NO synthase (NOS), in the retina of a teleost. NADPH diaphorase (NADPHd) histochemistry and NOS immunohistochemistry revealed both NOS immunoreactive and NADPHd positive structures in photoreceptor outer segments, amacrine cells, horizontal cells and ganglion cells. Since NO is known to stimulate the synthesis of cGMP, our results implicate an important role for NO in retinal function, especially in cGMP related events in the photoreceptors.

Amino Acid Oxidoreductases↗

PubMedDate not supplied

A neuromorphic model for achromatic and chromatic surface representation of natural images.

This study develops a neuromorphic model of human lightness perception that is inspired by how the mammalian visual system is designed for this function. It is known that biological visual representations can adapt to a billion-fold change in luminance. How such a system determines absolute lightness under varying illumination conditions to generate a consistent interpretation of surface lightness remains an unsolved problem. Such a process, called 'anchoring' of lightness, has properties including articulation, insulation, configuration, and area effects. The model quantitatively simulates such psychophysical lightness data, as well as other data such as discounting the illuminant, and lightness constancy and contrast effects. The model retina embodies gain control at retinal photoreceptors, and spatial contrast adaptation at the negative feedback circuit between mechanisms that model the inner segment of photoreceptors and interacting horizontal cells. The model can thereby adjust its sensitivity to input intensities ranging from dim moonlight to dazzling sunlight. A new anchoring mechanism, called the Blurred-Highest-Luminance-As-White rule, helps simulate how surface lightness becomes sensitive to the spatial scale of objects in a scene. The model is also able to process natural color images under variable lighting conditions, and is compared with the popular RETINEX model.

Adaptation, Ocular↗

PubMed1992

The physiology of GABAB receptors in the vertebrate retina.

Writing a chapter on retinal GABAB receptors is premature, as evidenced by the paucity of citations more than two years old. Despite that, this area of retinal pharmacology has made significant strides and, although it is a story without an ending, it has had an exciting beginning. To date, the experiments indicate that horizontal cell feedback to cones is mediated, at least in part, by the GABAB receptor system which probably regulates a potassium conductance. In the inner retina, GABAB receptors are found on bipolar cells, amacrines, and ganglion cells. Here, the actions are a subtle regulation of channel conductance, but the effects are a dramatic reorganization of a fundamental coding property of the retina, namely the distinction between tonic and phasic responses to light. In both the distal and proximal retina, the GABAB receptor does not appear to work alone, but instead works in concert with the GABAA receptor. The full significance of these interactions has yet to be determined. Although the discovery of the GABAB receptor has led to the resolution of several retinal mysteries, the case is far from closed. At this juncture, what can be said is that the GABAB receptor represents a unique and ubiquitous system that reveals the power of regulating calcium and potassium conductances, as opposed to the more familiar properties of the glutamate/acetylcholine regulated cationic conductances or the GABAA/glycine controlled chloride channels.

Animals↗

PubMed2000

Retinal ganglion cell topography in elasmobranchs.

Retinal wholemounts are used to examine the topographic distribution of retinal cells within the ganglion cell layer in a range of elasmobranchs from different depths. The retina is examined for regional specializations for acute vision in six species of selachians, Galeocerdo cuvieri, Hemiscyllium ocellatum, Scyliorhinus canicula, Galeus melastomus, Etmopterus spinax, Isistius brasiliensis, one species of batoid, Raja bigelowi and one species of chimaera, Hydrolagus mirabilis. These species represent a range of lifestyles including pelagic, mesopelagic and benthic habitats, living from shallow water to the sea bottom at a depth of more than 3000 m. The topography of cells within the ganglion cell layer is non-uniform and changes markedly across the retina. Most species possess an increased density of cells across the horizontal (dorsal) meridian or visual streak, with a density range of 500 to 2,500 cells per mm(2) with one or more regional increases in density lying within this specialized horizontal area. It is proposed that the higher spatial resolving power provided by the horizontal streak in these species mediates panoramic vision in the lower frontal visual field. Only I. brasiliensis possesses a concentric arrangement of retinal iso-density contours in temporal retina or an area centralis, thereby increasing spatial resolving power in a more specialized part of the visual field, an adaptation for its unusual feeding behavior. In Nissl-stained material, amacrine and ganglion cell populations could be distinguished on the criteria of soma size, soma shape and nuclear staining. Quantitative analyses show that the proportion of amacrine cells lying within the ganglion cell layer is non-uniform and ranges between 0.4 and 12.3% in specialized retinal areas and between 8.2 and 48.1% in the peripheral non-specialized regions. Analyses of soma area of the total population of cells in the ganglion cell layer also show that the pelagic species possess significantly smaller soma (9-186 micrometer(2)) than benthic and/or deep-sea species (16-338 micrometer(2)), and that a number of different morphological classes of cells are present including a small population of giant ganglion cells.

Animals↗

PubMed1999

A possible role for p16INK4 in neuronal cell death after retinal ischemia-reperfusion injury.

PURPOSE: To study whether cell type-specific death occurs in retinal ischemia-reperfusion injury and the possible roles of p16INK4 in the determination of cell death. METHODS: Retinal ischemia-reperfusion injury was induced in rats by a ligation method. After 1 hour of ischemia and a time of reperfusion that varied, rat eyes were enucleated. Cell death in the retina was studied by the TdT-dUTP terminal nick-end labeling method and propidium iodide (PI) staining. Electron microscopic observation of the retina was also performed. Immunohistochemical studies using antibodies against syntaxin and calbindin were performed to detect amacrine cells and horizontal cells, respectively, and immunohistochemical studies using an antibody against p16INK4 were performed to study whether this cell cycle-related protein was expressed in dying cells. RESULTS: Most of the calbindin-positive horizontal cells in the outer aspect of the inner nuclear layer (INL) showed morphologic features of necrosis. In contrast, syntaxin-positive amacrine cells in the inner aspect of the INL showed features of apoptosis. Of 320 calbindin-positive horizontal cells, only 11 (3.4%) showed positive PI staining. Those calbindin-positive, horizontal cells were p16INK4 positive. In contrast, 746 of 910 (82.0%) syntaxin-positive amacrine cells showed condensed PI staining, and none were p16INK4 positive. CONCLUSIONS: Expression of p16INK4 may regulate the fate of retinal neurons in ischemia-reperfusion injury, and cell type-specific death thus occurs in the retina after such injury.

Animals↗

PubMed1985

Rod-cone interactions and analysis of retinal disease.

Cone flicker threshold rises as the rods dark adapt, though the cone threshold to continuous light remains constant. The rise is normally about 1 log unit, but in certain patients who complain of night blindness it may be as great as 2.5 log units. In these persons the kinetics of the rod-cone interaction are those of the recovery of rod sensitivity. The rods impose a low-pass filter on the cones. This effect is absent in congenital nyctalopia and X-linked retinoschisis. We suggest that cone flicker is maintained through a feedback system involving horizontal cells, and when the rod dark current returns in dark adaptation this feedback is altered. Rod cone interaction thus tests rod dark current, and cases of abnormal interaction in patients with retinitis pigmentosa occur, which indicate that the transduction mechanism and the membrane dark current may be differentially affected.

Adolescent↗

PubMed2005

Cyclic AMP prevents retraction of axon terminals in photoreceptors prepared for transplantation: an in vitro study.

PURPOSE: Cell transplantation has emerged as a possible remedy for degeneration and injury in the central nervous system (CNS). In the retina, photoreceptor transplantation is a potential treatment for retinal degenerative disease. Graft survival has been well documented, but evidence of functional recovery is lacking. A major obstacle to recovery of vision is lack of synapse formation between grafted photoreceptors and host bipolar and horizontal cells. A prior study demonstrated that photoreceptors prepared for transplantation undergo rapid morphologic changes, including retraction of axon terminals toward their cell bodies, away from potential synaptic partners, a phenomenon that may interfere with graft-host synaptic interaction after transplantation. In this study, prevention of retraction of photoreceptor axon terminals was possible by pharmacological intervention. METHODS: Photoreceptor sheets, prepared by vibratome sectioning, and full-thickness retinas, harvested from adult porcine eyes, were maintained in culture and treated with either the cyclic adenosine monophosphate analogue 8-(4-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (CPT-cAMP), or forskolin, an adenylyl cyclase stimulant, for up to 48 hours. RESULTS: Both CPT-cAMP and forskolin treatments successfully blocked retraction of photoreceptor axon terminals. This effect was not due to cell toxicity and was reversed after removal of treatment, indicating its specificity. CONCLUSIONS: Pharmacological manipulation of photoreceptor axonal plasticity may improve graft-host synaptic interaction after subretinal photoreceptor cell transplantation.

Adenylyl Cyclases↗

PubMed1996

Maturational gradients in the retina of the ferret.

In the present set of studies, we have examined the site for the initiation of retinal maturation in the ferret. A variety of maturational features across the developing inner and outer retina were examined by using standard immunohistochemical, carbocyanine dye labelling, and Nissl-staining techniques, including 1) two indices of early differentiation of the first-born retinal ganglion cells, the presence of beta-tubulin and of neuron-specific enolase; 2) the receding distribution of chondroitin sulfate proteoglycans within the inner retina; 3) the distribution of the first ganglion cells to grow axons along the optic nerve; 4) the emergence of the inner plexiform layer; 5) the emergence of the outer plexiform layer and 6) the onset of synaptophysin immunoreactivity within it; 7) the differentiation of calbindin-immunoreactive horizontal cells; and 8) the cessation of proliferative activity at the ventricular surface. Although we were able to define distinct maturational gradients that are associated with many of these features of inner and outer retinal development (each considered in detail in this report), with dorsal retina maturing before ventral retina, and with peripheral retina maturing last, none showed a clear initiation in the region of the developing area centralis. Rather, maturation began in the peripapillary retina dorsal to the optic nerve head, which is consistent with previous studies on the topography of ganglion cell genesis in the ferret. These results make clear that the order of retinal maturation and the formation of the area centralis are not linked, at least not in the ferret.

Animals↗

PubMed2002

Inner-retinal contributions to the photopic sinusoidal flicker electroretinogram of macaques. Macaque photopic sinusoidal flicker ERG.

The purpose of this study was to examine inner-retinal contributions to the photopic sinusoidal flicker ERG. ERGs were recorded from 5 anesthetized monkeys to sinusoidally modulated (100%, 0.5-120 Hz) red full field flicker at Lmean of 3.2 log phot td on a rod saturating blue background (3.7 log scot td; 3.0 log phot td) before and after intravitreal injections of tetrodotoxin (TTX) to block Na+-dependent spikes of retinal ganglion and amacrine cells, followed by N-methyl-D-aspartate (NMDLA) to suppress all activity of these cells. Recordings also were made after blocking bipolar (and horizontal) cell responses with L-2-amino-4-phosphonobutyric acid (APB) and 2-cis-piperidine-2,3-dicarboxylic acid (PDA) or 6-cyano-nitroquinoxaline-2,3-dione (CNQX). Control fundamental (F1) and second harmonic (F2) amplitudes were large and variable at temporal frequencies up to 2 Hz. At higher frequencies, Fl amplitude was minimal with a phase step at a frequency between 13 and 19 Hz and maximal at 27-33 Hz. F2 was minimal at 2-3 Hz and maximal at 6-8 Hz, again with a phase step near the minimum. TTX, or NMDLA, produced small changes in Fl that shifted the amplitude minimum to a lower and the maximum to a higher frequency. In contrast, F2 was more strongly affected; both the amplitude minimum (and phase step) and maximum were greatly attenuated, leaving a moderate response from 0.5 to 8 Hz, which then declined as frequency was increased to 30 HZ. After APB and PDA or CNQX, F1 decreased continuously with increasing frequency and F2 was generally much smaller. The nearly linear F1 phase plotwas consistent with the presence of a single mechanism (i.e. photoreceptors). Inner-retinal neurons contribute to the photopic sinusoidal flicker ERG. Whereas for F1, inner-retinal contributions are small relative to those from bipolar cells; for F2, they are equal or greater between 2and 16 Hz.

6-Cyano-7-nitroquinoxaline-2,3-dione↗