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High-pass resolution perimetry: central-field neuroretinal correlates.

Minimum angles of resolution (MAR) were measured at 0-10 deg horizontal eccentricity in three normal subjects, using high-pass spatial frequency filtered targets, at four different contrast levels. Results were correlated with recent data on human cone and ganglion cell separations in corresponding retinal locations. MARs and cone separations showed a close proportionality through the origin for all contrast levels. Ganglion cell correlates were more difficult to elucidate as the cell bodies are displaced from their input cones. Taking a functional estimate of the displacement into account, the number of ganglion cells appeared to be large enough to uphold an "effective" distribution that obeys the same proportional relationship to MAR that previously has been demonstrated outside 10 deg. Analysis of the nature of age effects provided support for this model.

Adult↗

S-potentials in the dark-adapted retina of the carp.

1. S-potentials were recorded in the dark-adapted carp retina. After recording, Procion Yellow was injected from the recording electrode to identify histologically the cell recorded.2. Both L- and C-type S-potentials were found. L-type S-potentials were further classified into two groups. The first group was characterized by a high threshold, fast rise and fall times and a spectral sensitivity peak of about 620 nm. The second group showed a low threshold, slow response time course and a spectral sensitivity peak of about 520 nm.3. Cells of the first group were identified as external and internal horizontal cells. Cells of the second group were identified as intermediate horizontal cells.4. In the dark-adapted retina, the spectral sensitivity of the intermediate horizontal cell showed a good agreement with the absorption spectrum of the rod pigment, porphyropsin.5. Neither a chromatic background nor white background illumination of moderate intensity (1 cd.m(-2)) shifted the spectral sensitivity of the intermediate horizontal cell.6. Under a strong background (10 cd.m(-2)), the intermediate horizontal cell was entirely suppressed. Under the same conditions the external horizontal cell was still capable of responding.7. From these observations it is concluded that the intermediate horizontal cell receives input from rods only.

Action Potentials↗

[Physiologic principles of studying visual functions].

The retinal coding system for visual information comprises three important steps: 1) hyper- and depolarization of the sensory cells as the active basis for perception of light and dark; 2) reaction solely to changes in the bipolar cell on/off system, as a consequence of the action of the horizontal cells with the receptive fields, as a basis for adaptation to brightness and glare; and 3), under the influence of the amacrine cells, important time-space functions as a basis for visual perception of movement. The signal form, which changes over from analog to digital in the ganglion cell system, also results from this last step. therefore, both latencies and amplitudes (VEP) are important criteria for long signal response paths. Taking the examples of "statistical perimetry", visual acuity testing, and examination of contrast sensitivity, clinically relevant methodological problems from signal detection theory are illustrated: there are no "certain" measured values. This uncertainty and the age-dependence of normal values make it difficult to identify pathologic conditions, though trend analyses can help. As the sizes of the retinal areas examined by these methods differ so widely, correlations between the various examination methods are theoretically possible; but one method can never be substituted by another. In routine practice, to detect pathology early, one will sometimes deviate from the prescribed examination method (vision tests with low contrast for visual acuity).

Dark Adaptation↗

TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo.

Injury-induced downregulation of neurotrophin receptors may limit the response of neurons to trophic factors, compromising their ability to survive. We tested this hypothesis in a model of CNS injury: retinal ganglion cell (RGC) death after transection of the adult rat optic nerve. TrkB mRNA rapidly decreased in axotomized RGCs to approximately 50% of the level in intact retinas. TrkB gene transfer into RGCs combined with exogenous BDNF administration markedly increased neuronal survival: 76% of RGCs remained alive at 2 weeks after axotomy, a time when >90% of these neurons are lost without treatment. Activation of mitogen-activated protein kinase, but not phosphatidylinositol-3 kinase, was required for TrkB-induced survival. These data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.

Animals↗

Endothelin receptors in light-induced retinal degeneration.

Excessive light exposure leads to retinal degeneration in albino animals and exacerbates the rate of photoreceptor apoptosis in several retinal diseases. In previous studies we have described the presence of endothelin-1 (ET-1) and its receptors (ET-A and ET-B) in different sites of the mouse retina, including the retinal pigment epithelium, the outer plexiform layer (OPL), astrocytes, the ganglion cell layer (GCL), and vascular endothelia. After light-induced degeneration of photoreceptors, endothelinergic structures disappear from the OPL, but ET-1 and ET-B immunoreactivities increase in astrocytes. Here, we present novel observations about the course of light-induced retinal degeneration in BALB-c mice exposed to 1500 lux during 4 days with or without treatment with tezosentan, a mixed endothelinergic antagonist. Retinal whole mounts were immunostained with anticleaved caspase-3 (CC-3) serum to identify apoptotic photoreceptor cells within the outer nuclear layer (ONL). Glial activation was measured as glial fibrillary acidic protein (GFAP) immunoreactivity in retinal whole mounts and in Western blots from retinal extracts. Tezosentan treatment significantly reduced both the number of CC3-immunoreactive cells and GFAP levels, suggesting that inhibition of endothelinergic receptors could play a role in photoreceptor survival. Using confocal double immunofluorescence, we have observed that ET-A seems to be localized in bipolar cell dendrites, whereas ET-B is localized in horizontal cells. Our observations suggest the existence of an endothelinergic mechanism modulating synaptic transmission in the OPL. This mechanism could perhaps explain the effects of tezosentan treatment on photoreceptor survival.

Animals↗

Potentiation of transmitter release by protein kinase C in goldfish retinal bipolar cells.

1. We examined whether transmitter release could be modified by the activation of protein kinase C (PKC) of retinal bipolar cells. A bipolar cell with a large axon terminal was isolated from the goldfish retina. The presynaptic Ca2+ current was measured under whole-cell voltage clamp, and the released transmitter (probably glutamate) was detected electrophysiologically by using the response of NMDA receptors of catfish horizontal cells as a reporter. 2. Transmitter release was potentiated by a PKC activator, phorbol 12-myristate 13-acetate (PMA), but not by an ineffective phorbol ester, 4alpha-phorbol 12,13-didecanoate. A PKC inhibitor, bisindolylmaleimide I, did not affect the transmitter release by itself but blocked the PMA-induced potentiation of transmitter release. These results suggest that the actions of PMA were mediated via the activation of PKC. 3. Introduction of 5 mM EGTA into the presynaptic terminals of bipolar cells revealed two separate components of transmitter release. A rapid component was triggered immediately after depolarization while a slow component appeared with a delay. Application of PMA selectively potentiated the slow component without affecting the Ca2+ dependence of exocytosis. 4. We suggest that the activation of PKC may modify the recruitment process of synaptic vesicles in retinal bipolar cells.

Animals↗

Computational studies on the interaction between red cone and H1 horizontal cell.

We propose an equivalent circuit model of a discrete formulation to describe the interaction between the red cone syncytium and the H1 horizontal cell syncytium in lower vertebrate retinas. Analytical solutions of the model provide intuitive understandings of spatio-temporal properties of light-induced responses in reference to membrane impedance, strength of chemical synapse and coupling resistance connecting neighbouring cells. Physiologically plausible values of these parameters are estimated using the solutions. Quantitative studies are made to elucidate the function of (1) the negative feedback from the H1 horizontal cell to the red cone, and (2) the resistance increase of H1 horizontal cell coupling by dopamine.

Animals↗

GDNF regulates chicken rod photoreceptor development and survival in reaggregated histotypic retinal spheres.

PURPOSE: To investigate the role of glial-cell-line-derived neurotrophic factor (GDNF) on proliferation, differentiation, and apoptosis of different retinal cell types--in particular, photoreceptor cells. METHODS: Reaggregated histotypic spheres, derived from retinal cells of the E6 chicken embryo were used. Under rotation, so-called rosetted spheroids arose by aggregation of dissociated retinal cells, followed by the proliferation, migration, differentiation and programmed cell death of particular cell types. Rosetted spheroids were cultured under serum-reduced conditions, either in the absence or presence of 50 ng/mL GDNF. At appropriate stages, rosetted spheroids were analyzed by using conventional staining and immunolabeling with antibodies against different retinal cell types. RESULTS: At early stages of culture, the application of GDNF to rosetted spheroids significantly increased and sustained the rate of proliferation. In particular, a de novo production of rod photoreceptors was observed, whereas cone photoreceptors and amacrine, horizontal, ganglion, and Müller cells were not affected. In addition, in GDNF-treated cultures, rod photoreceptors differentiated earlier than in nontreated cultures. In older rosetted spheroids raised in absence of GDNF, rod but not cone photoreceptors underwent apoptosis. By supplementation with GDNF, the percentage of dying rod photoreceptors was dramatically reduced (31%-6% at 8 days in culture, 71%-3% at 10 days in culture). Both the mitogenic and survival promoting effect of GDNF were dose dependent. CONCLUSIONS: The results strongly suggest that GDNF, at least in vitro, affects rod photoreceptors. Depending on the developmental stage, GDNF regulates their proliferation, differentiation, and survival.

Animals↗

Anatomical pathways for color vision in the human retina.

The major neurons and neural circuits that are involved in the transmission of color signals through the human retina to produce the color and spatially opponent P cell or midget ganglion cell responses are described. The older findings of single cone to midget bipolar connectivity is reviewed, and the single midget bipolar cell to midget ganglion cell connectivity as revealed by a recent serial section electron microscope study is described in detail. Our present knowledge concerning the discrimination of the blue-cone subtype from the other longer wavelength cones in the human at the outer plexiform layer is summarized, and our most recent findings concerning horizontal cell connectivity to the different spectral types of cones are discussed. Finally, a hypothetical pathway is proposed for color-opponent surrounds of midget ganglion cells using both horizontal cells at the outer plexiform layer and amacrine cell pathways at the inner plexiform layer.

Axons↗

Spatial organizations of catfish retinal neurons. II. Circular stimulus.

1. Temporal dynamics of receptive-field components were identified by use of circular stimuli whose diameter was modulated in white-noise fashion. 2. A thin ring of light evoked a complex response from the horizontal-cell soma but not from its axon. 3. All bipolar cells had a biphasic receptive field whose incremental sensitivities were comparable for the field's center and surround. 4. Type-N cells had a biphasic field whose two components were segregated both in time and space. 5. Type-C cells showed nonlinearities, which did not depend on the types of light inputs and which were intrinsic to the cell. 6. Ganglion cells could be classified roughly into two classes: small- and large-field cells. Their main nonlinearity was rectification. 7. Our studies on the catfish retna have shown that the distal cells are essentially linear in time and space and can be identified functionally by any type of input. The proximal cells, however, have a complex functional repertoire whose identification poses considerable difficulty.

Animals↗

Signal transmission in the catfish retina. I. Transmission in the outer retina.

Extrinsic current, either pulsatile or white-noise modulated, was injected into the (cone) horizontal-cell soma and axon, and resulting responses were recorded from nearby points. In the case of white-noise inputs, signal transmission between the two points was characterized by Wiener kernels. The signal transmission within the lamina, the S-space, formed by the (cone) horizontal-cell somas and axons is quasi-linear and very fast, indicating that the laminae are purely resistive networks within the frequency range of the light-evoked response. There exists signal transaction between the lamina formed by the somas and axons. The forward transmission is constant gain, low pass, but there is a filter for the reverse transmission to impede the backflow of high-frequency components. Signals in the horizontal-cell soma are transmitted to the bipolar cells. The transmission is sign noninverting for the on-center bipolar cells and sign inverting for the offcenter cells. The transmission is quasi-linear excluding complex mechanisms in the transmission. We believe that the forward and direct transmission of signals from the horizontal to bipolar cells is the most straightforward interpretation of the observation. The transfer functions between the horizontal and bipolar cells differ considerably from one bipolar cell to the next.

Animals↗

Somatostatin receptor subtype 2A expression in the rat retina.

Somatostatin is mainly expressed by sparsely occurring amacrine and interplexiform cells in the retina. In this study, we characterized the expression and cellular localization of one of the somatostatin subtype (sst) receptors, sst2A, in the rat retina. The presence of sst2A receptor messenger RNA in retinal extracts was demonstrated by reverse transcription-polymerase chain reaction using specific primers to detect the sst2 receptor and its isoforms, sst2A and sst2B. Specific sst2A receptor immunoreactivity was mainly localized to the plasma membrane of several neuronal cell types. In the outer retina, immunoreactivity was localized to cone photoreceptors, horizontal cells, and rod and cone bipolar cells. Double-label experiments showed the co-localization of sst2A receptor and protein kinase C (alpha and beta), a rod bipolar cell marker, and of sst2A receptor and Calbindin-D28k, a horizontal cell marker. In the inner retina, sst2A receptor immunoreactivity occurred in tyrosine hydroxylase-positive amacrine cells; most were of medium to large size. These findings indicate that somatostatin may act at a distance, in a paracrine manner, on several cell types that express the sst2A receptor, and therefore exert a broad modulatory influence on both scotopic and photopic visual pathways.

Animals↗

The development of astrocytes and blood vessels in the postnatal rabbit retina.

Antibodies to glial fibrillary acidic protein (GFAP) have been used to study the shape and location of astrocytes in whole mount preparations of developing postnatal rabbit retina. At all developmental stages GFAP-positive astrocytes were detectable. At birth, they were few in number and only weakly labelled. With further development, their number as well as their labelling intensity increased. Following Nissl counterstaining it was observed that GFAP-positive astrocytes, always situated in the nerve fibre layer, are capable of cell division during about the first 4 postnatal weeks. GFAP-positive astrocytes were always confined to a wing-shaped area extending horizontally from both sides of the optic nerve head. It is suggested that astrocytes are not generated in the entire rabbit retina, which is in clear contrast to the second glial cell type of the rabbit retina, the Müller cell; and it has been concluded that the confinement of astrocytes to the medullary rays region in the adult rabbit is established during ontogenesis, and is not due to a secondary restriction of astrocytes to this region. Horizontal sections cut through entire rabbit retinae at various postnatal stages revealed that the first intraretinal blood vessels are not found before postnatal day 9. This is more than 1 week later than the first astrocytes are detectable. It is suggested that, at least in the rabbit, retinal astrocytes do not co-migrate with blood vessel endothelial cells from the optic disc into the retina, a hypothesis considered recently for the cat retina. It was, however, not possible to decide unequivocally if, in this material, astroglial progenitors are derived from retinal neuroepithelial cells or invade the retina from the optic nerve head.

Animals↗

Development of cell markers in subretinal rabbit retinal transplants.

Retinas from embryonic rabbits at day E15 were transplanted to the subretinal space in adult rabbits. After survival times between 7 and 193 days, the rabbits were killed, and the transplants were processed for immunohistochemistry. The results show that subretinal transplants from embryonic rabbit retinas develop many, if not all, retinal neuronal types. The cells show approximately normal morphology and express a variety of cell-type-specific markers: photoreceptor cells express visual pigment proteins as identified by antibodies against rhodopsin (R2-15), color-specific cone pigments (COS-1, OS-2) and the cone specific antigen 50-1B11, rod bipolar cells express PKC, horizontal cells HPC-1 antigen and neurofilament 160 kDa, amacrine cells HPC-1 antigen, GABA and neurofilament 160 kDa, and glial cells express vimentin and glial fibrillary acidic protein. The high degree of rosette formation seen in many young grafts, diminishes with time; many transplant cells disappear, and the remaining cells present a less prominent formation of rosettes.

Animals↗

The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina.

We examined the contribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid (AMPA)/kainate (KA) receptors to the light-responses of rabbit retinal neurons. In the outer retina, bath application of the AMPA/KA receptor antagonists 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and 2,3,dihydroxy-6-nitro-7-sulfamoyl-benzo-f-quinoxaline (NBQX) blocked the light-responses of horizontal cells. Application of quinoxalines enhanced ON-bipolar cell light-responses, and was associated with a hyperpolarization of their resting potentials. In the inner retina, application of both AMPA/KA and NMDA antagonists to AII amacrine-like cells only partially blocked their light-responses. Their residual responses may reflect electrical coupling to neighboring ON-center cone bipolar cells, and can inhibit OFF-center ganglion cells. ON-sustained ganglion cells were highly sensitive to the quinoxalines, which reduced their light-evoked firing, while the firing of ON-transient cells remained as NMDA-mediated light-responses. Quinoxalines had differential effects on the firing rates of ON- and OFF-center ganglion cells: ON-cells were reduced, while OFF-cells were increased. In contrast, firing rates of ON-OFF ganglion cells were not excited by NBQX, and showed a recovered light-response mediated by NMDA receptors. The receptive field surround was lost in ganglion cells. For comparison, NMDA antagonists had only moderate effects on all ganglion cell light-responses. Our results indicate that NMDA and AMPA/KA receptors both contribute to ganglion cell light-responses. However, AMPA/KA receptors also significantly effect the light-response of neurons presynaptic to retinal ganglion cells, altering the observed pharmacology at the ganglion cell level.

Animals↗

Human albinism. Light and electron microscopy study.

The eyes of a 13-year-old leukemic boy with the attributes of tyrosinase-negative oculocutaneous albinism were obtained for light and electron microscopic study. Repeated examinations had failed to reveal WBCs with giant oxidase-positive granules, and leukemic involvement of the fundus never occurred. Light microscopic examination of horizontal and vertical sections through the retina confirms earlier reports that the fovea is absent in albinos. The synaptic apparatus of the photoreceptor terminals appears abnormal. The rough endoplasmic reticulum of the retinal pigment epithelial cells is sparse though the presence of phagosomes suggests that phagocytic function is intact. Suggestions as to the importance that the morphological findings may have on albino visual function are made.

Acute Disease↗

Adaptability of the vestibulo-ocular reflex to vision reversal in strobe reared cats.

Optical reversal of vision brings about adaptive changes in the vestibulo-ocular reflex (VOR) tending to reduce retinal image slip during head movement. The present experiments investigated this form of adaptation in cats whose complement of direction sensitive central visual cells had been substantially reduced by rearing in 8 Hz stroboscopic light. Horizontal vision reversal was produced by dove prisms carried in a skull-mounted mask. A scleral eye coil was used to measure horizontal eye movements. VOR gain and phase were measured in the dark during sinusoidal rotation using test stimuli of 1/8 Hz and 5- or 20 degrees/sec velocity amplitude. Initially, strobe reared cats produced virtually normal VOR in the dark, except for slight but significant exaggeration of the normal phase advancement to be expected at 1/8 Hz. Addition of their familiar strobe illumination produced almost perfect oculomotor compensation. Maintained vision reversal in both strobe and normal illumination produced similar patterns of adaptive change in normal and strobe reared subjects, i.e. all animals exhibited an initial fast, and subsequent much slower, stage of gain attenuation, with similar changes in phase. Thus, strobe rearing did not prevent the development of an essentially normal VOR, nor did it interfere significantly with the ability to adapt in response to vision reversal. Since strobe rearing depletes direction selective visual movement detectors in the cortex and superior colliculi, it is inferred that signals responsible for activating the adaptive process are probably carried mainly in the accessory optic, rather than cortical and collicular, visual system.

Animals↗

GABA neurones in retinas of different species and their postnatal development in situ and in culture in the rabbit retina.

The localisation of GABA immunoreactive neurones in retinas of a variety of animals was examined. Immunoreactivity was associated with specific populations of amacrine neurones in all species examined, viz. rat, rabbit, goldfish, frog, pigeon and guinea-pig. All species, with the exception of the frog, possessed immunoreactive perikarya in their retinal ganglion cell layers. These perikarya are probably displaced amacrine cells because GABA immunoreactivity was absent from the optic nerves and destruction of the rat optic nerve did not result in degeneration of these cells. GABA immunoreactivity was also associated with the outer plexiform layers of all the retinas studied; these processes are derived from GABA-positive horizontal cells in rat, rabbit, frog, pigeon and goldfish retinas, from bipolar-like cells in the frog, and probably from interplexiform cells in the guinea-pig retina. The development of GABA-positive neurones in the rabbit retina was also analysed. Immunoreactivity was clearly associated with subpopulations of amacrine and horizontal cells on the second postnatal day. The immunoreactivity at this stage is strong, and fairly well developed processes are apparent. The intensity of the immunoreactivity increases with development in the case of the amacrine cells. The immunoreactive neurones appear fully developed at about the 8th postnatal day, although the immunoreactivity in the inner plexiform layer becomes more dispersed as development proceeds. The immunoreactive horizontal cells become less apparent as development proceeds, but they can still be seen in the adult retina. The GABA immunoreactive cells in rabbit retinas can be maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗