Search PubMed⌕ Search

Biomedical subjects

A R Adolph

Publications and source records attributed to A R Adolph.

At least 19 recordsLinked to original sources
PubMed1994

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↗
PubMed1994

Spectral and pattern response in the rabbit retina.

The advantages of presenting sensory data in terms of stimulus variables are stressed. Spectral sensitivity plots of local electroretinograms and ganglion cell discharges from the dark-adapted rabbit retina illustrate the utility of using this kind of procedure. Spectral data agreed with the literature demonstrating two cone and one rod process in this animal. The spectral sensitivities of both the local electroretinogram and ganglion cell spikes were closely similar. Data pertaining to pattern vision may also be subjected to the same type of analysis and described in terms of stimulus variables.

Animals↗
PubMed1992

Transplantation of embryonic retina to the subretinal space in rabbits.

Embryonic rabbit retina can be transplanted to the subretinal space of adult rabbit with a new method, which gives a high rate of successful short-term transplants. Embryonic (stage E 15) neural retina cells were injected through an incision just behind the sclerocorneal border with a thin (inner diameter 0.15-0.4 mm, outer diameter 0.3-0.5 mm) plastic tube attached to a specially designed instrument, by which the length of the protruding plastic tip could be controlled. The retina was penetrated from the vitreous side and the donor tissue was injected into the subretinal space. The cells survived in the host for at least 5 months, although the long-term survival rate tended to decrease. The transplanted cells matured and differentiated, forming an approximation of the layered, retinal structure with some anomalies (e.g. rosettes). The subretinal location offers an interesting and convenient way of studying the development of retinal cell transplants in rabbits. Large transplants can be produced, and the risk for failures due to erroneous vitreous placement is small.

Animals↗
PubMed1991

Ultrastructure of human retinal cell transplants with long survival times in rats.

Human fetal retinas (6-12 weeks post-conception) were obtained from elective abortions, transplanted to rat retinas and examined by electron microscopy. The oldest transplants that form the basis of this report were obtained 40 and 41 total weeks post-conception. The host rats were immunosuppressed with cyclosporin A. The transplants developed according to their intrinsic, genetically determined timetable. The development was heterogeneous with some parts showing almost normal differentiation and others, little. Both rods and cones developed with inner and outer segments and synaptic terminals. In regions corresponding to the inner plexiform layer, bipolar cell processes were seen in the typical dyad arrangement. Likewise, amacrine cell processes formed typical conventional synapses. Serial synapses were seen, engaging amacrine cell synapses as well as a few reciprocal synapses at the bipolar cell dyads. Monad-type synaptic complexes, a sign of immaturity, were common in bipolar cell processes. Similarly, incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed. Ganglion cell processes could not be identified with certainty. A structure with morphological characteristics similar to the inner limiting membrane was noted to form inside the transplant. Both epi-retinal and sub-retinal transplants were obtained. Transplant cells touched host photoreceptor cells or pigment epithelium without any obvious specializations. The host pigment epithelium microvilli were absent adjacent to the graft. However, graft cells did appear in the host retina, and nerve cell processes were observed to cross the membrane separating the transplant and host.

Animals↗
PubMed1991

Spatial properties of ganglion cell activity in the turtle retina.

Ganglion cell activity in response to drifting or alternating stimulus patterns was recorded in an eyecup preparation of the turtle. The stimuli were sinusoidal gratings with various spatial frequencies and spatial phases. Spike histograms of the activity were Fourier-analyzed. The results indicated that the retinal circuitry always functioned in a nonlinear manner. The average, first, and second harmonics of the activity were all a function of stimulus conditions, including spatial phase. Similar outcomes were obtained with full-field (retina-wide) and a small-field (1 mm diameter) stimulation. In the middle of the spatial-frequency range, the ratio of second to first harmonic activity was higher in response to static, contrast-reversing gratings than for drifting, constant-contrast ones. The findings suggest that, as distinct from the usual X, Y, and W segregation of ganglion cell properties in other retinas, there is a single class of cells whose responses seem to have attributes of one or another of the usual categories depending on stimulus characteristics. This may be the result of a degree of stimulus-dependent functional modification in the retinal input circuitry to the turtle ganglion cells.

Animals↗
PubMed1990

Neuronal markers in rat retinal grafts.

Rat E15 retina was grafted to the retina of adult rat hosts. After varying survival times (1 week-6 months), grafts were stained by immunohistochemistry for neurofilament 160 kDa (NF), HPC-1 (an amacrine cell marker), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and somatostatin-28 (SS-28). The first differentiating graft amacrine cells (cholinergic and dopaminergic) could be seen 1 week after transplantation (corresponding to postnatal day 1 = P1). The inner plexiform layer of the graft started to differentiate at 2 weeks (corresponding to P8) seen by HPC-1 and GAD staining. ChAT, TH and SS-28 immunostaining revealed an abnormal lamination pattern in the graft inner plexiform layer. Also by 2 weeks, the outer plexiform layers of the graft contained NF-immunoreactive horizontal cells. No NF-stained retinal ganglion cells could be observed in the graft. Five and 7 weeks after grafting, the transplants had obtained the same staining intensity with different markers as the host retina.

Animals↗
PubMed1990

Local pattern electroretinograms and ganglion cell activity in the turtle eye.

1. Local electroretinograms and spike activity from ganglion cells were recorded from an eye cup preparation of the turtle retina. The responses were elicited with striped and plaid stimulus patterns. 2. The results obtained with the two forms of recording were highly similar. Both depended on the spatial phase of the pattern with respect to the recording electrode. Both had maximal response at the same stimulus spatial frequency. 3. The optimum spatial frequency (both for maximum electroretinogram amplitudes and spike discharge rates) shifted to lower values with the administration of the GABA antagonist, picrotoxin. 4. The low frequency falloff associated with this spatial tuning may point to a mechanism of lateral interactions common to the local electroretinogram and spike responses.

Animals↗
PubMed1989

Pharmacological actions of peptides and indoleamines on turtle retinal ganglion cells.

In the turtle retina the peptides met-enkephalin (metENK), somatostatin (SS), neurotensin (NT), and the indoleamine serotonin (5-HT) modulate ganglion cell (GC) activity. The predominant action of the peptides is excitatory, generally enhancing spontaneous firing and light-evoked activity. In contrast, 5-HT usually inhibits these GC activities. MetENK has both direct synaptic input onto GC and indirect action possibly via a GABA inhibitory interneuron. The metENK actions appear mediated via a mu-opiate receptor; morphine and D-ala-metENK-amide (DALA), a stable analog of metENK, are agonists. Naloxone antagonizes the actions of metENK and its agonists. DALA occasionally inhibits GC. This inhibition is antagonized by picrotoxin, while concurrent excitatory action on GC is enhanced. DALA enhances GC response at high spatial frequencies; naloxone attenuates it. The enhancement by DALA suggests a narrowed receptive-field (RF) center, possibly due to changes in a GABA-mediated inhibitory surround. 5-HT inhibitory actions are also mediated via direct and indirect synaptic pathways. 5-methoxy-dimethyl-tryptamine and methoxy-phenyl-piperazine are agonists of 5-HT action. They are both specific 5-HT1 agonists. LSD (lysergic acid diethylamide) and cyproheptadine, which act on 5-HT2 receptors, antagonize 5-HT actions in this retina. Strychnine enhances GC activity, probably by antagonizing glycine-mediated inhibitory inputs. It does not block the inhibitory action of 5-HT, which suggests that the indirect 5-HT inhibition is not mediated via a glycinergic interneurone. 5-HT suppresses directional selectivity (DS) and attenuates high spatial frequencies in some GC. This may be mediated via inhibition of GABAergic amacrines subserving DS and the RF inhibitory surround.

Animals↗
PubMed1988

Center-surround, orientation, and directional properties of turtle retinal horizontal cells.

The spatial transfer functions (STF) of L-type horizontal cells (HC) in turtle retina were measured using drifting sine wave grafting stimuli. Two classes of STF were identified: low-pass and band-pass. A low-pass STF corresponds to a linespread function (LSF) having an excitatory center that attenuates monotonically with distance; a band-pass STF corresponds to a LSF with an excitatory center and an inhibitory surround. Two models of the surround inhibitory mechanism, based on retinal outer plexiform layer (OPL) anatomy, are tested experimentally: surround mediated lateral inhibition and surround modulated self-inhibition. In both types, sign inverting pathways are based on GABA feedback synapses, and sign conserving pathways are based on excitatory synapses and gap junctions. Temperature variation was used to modify synaptic properties and study their effect on STF. The low frequency limb of band-pass STF was most sensitive to temperature changes; its slope increased with decreasing temperature. Synaptic properties were also manipulated pharmacologically. Cutoff frequency of low-pass STF decreased from 0.5 to 0.4 cpmm during exogenous GABA. Picrotoxin (PTX) increases upper cutoff frequency and decreases low frequency limb slope in band-pass STF. Band-pass STF of a ganglion cell (GC) has higher upper and lower cutoff frequencies than a HC in the same retinal region, which corresponds to strong spatial convergence from HC to GC. Orientation sensitivity and directional selectivity were found in some HC. Differences between major and minor response axes in orientation sensitive HC were small, ca. 2 dB; orientation differences in directionally selective HC were also small (ca. 1-2 dB) but directional asymmetry was large (ca. 10-12 dB).

Animals↗
PubMed1985

Temporal tuning and nonlinearity of intraretinal pathways in turtle: effects of temperature, stimulus intensity, and size.

Flash responses, amplitude and phase transfer functions, and nonlinearities were measured in turtle retina for pathways with photoreceptor inputs and outputs from horizontal (HC), hyperpolarizing bipolar (HBC), sustained amacrine (AC), and on-off ganglion (GC) cells. Flash responses slowed and attenuated in all cells as temperature decreased. White-noise transfer properties of sustained-type cells (HC, HBC, AC) were of low- or bandpass type; high-frequency cut-off (fc) and phase crossover frequency decreased with temperature. fc increased as spot diameter was increased. Nonlinearity of these sustained-response pathways (distortion product frequencies in response to a sum-of-sinusoids input probe) increases with intensity and may depend on amplitude saturation limiting. On/off GC synaptic and spike activity increased as spot diameter decreased and intensity increased. Amplitude transfer functions had a low-frequency peak (PSP activity) and monotonically decreasing amplitude vs. frequency shape (spikes and transient PSP activity). Nonlinearity increased with stimulus intensity; it was maximal with 1 mm spot size, less with smaller (500 micron) and larger (5 mm) spots. It may depend on the functional equivalent of full-wave rectification (on-off response).

Animals↗
PubMed1985

Temporal transfer and nonlinearity properties of turtle ERG: tuning by temperature, pharmacology, and light intensity.

ERG impulse response, amplitude and phase temporal spectral transfer functions, and nonlinearities were measured in turtle retina under different retinal temperatures, pharmacological treatments, and light intensities. beta-Wave amplitude is strongly temperature dependent; amplitudes of the alpha-wave and slow P-III are less sensitive. Their time courses all slow markedly as temperature decreases. ERG amplitude transfer function is bimodal bandpass with narrow low-frequency peak (below 1 Hz) and broader mid-frequency peak (5 Hz at 8 degrees C). Both peaks broaden and their frequency increases (low, 1 Hz; mid, 15 Hz, at 23 degrees C) as temperature increases. Phase transfer function slope decreases (from -70 degrees/Hz at 8 degrees C to -25 degrees/Hz at 23 degrees C) as temperature increases. Nonlinear properties of ERG at high input intensity are modelled by a quadratic nonlinearity, low-pass prefilter with cutoff above 12.4 Hz, and low-pass postfilter broadly peaked at 6-10 Hz with cutoff above 20 Hz. For low input intensity, ERG exhibits linear properties with low-pass filtering sharply cut off above 6 Hz. alpha-Wave and slow P-III were isolated by aspartate treatment; depolarizing bipolar cell activity was examined using ethanol/GABA treatment of retina. High-frequency components, including broad mid-frequency peak, were attenuated and low-frequency components were enhanced with aspartate. Transfer function narrows and peaks at a lower frequency with ethanol/GABA.

Animals↗
PubMed1985

Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells.

Synaptic drugs were superfused into turtle eyecup preparation while recording extracellularly from directionally sensitive (DS) retinal ganglion cells. As in previous experiments in intact rabbit retina, both picrotoxin (a GABA antagonist) and physostigmine [an acetylcholine (ACh) potentiator] reduced or eliminated the directional selectivity of these cells. These drug effects occurred at micromolar concentrations and were long lasting. Superfusion of ACh caused excitation, and GABA caused inhibition of the spike activity of these DS cells. In some experiments, the ganglion cell was isolated from its presynaptic inputs by perfusing with a low-Ca2+/EGTA perfusate, which blocked synaptic transmission but did not suppress spike firing. During this synaptic block, ACh still caused spontaneous spike firing, and GABA was able to suppress the ACh-induced spike activity. Strychnine slightly increased the spontaneous activity of DS ganglion cells and reduced their response to light. Glycine and taurine were equally effective in totally suppressing spike activity, and strychnine blocked this inhibition by both agents. However, these inhibitory effects may be transynaptic because glycine did not suppress ACh-induced excitation during synaptic block. Superfusion of micromolar concentrations of methionine enkephalin and [D-Ala2]methionine enkephalinamide occasionally caused small increases in the light responses of DS cells, whereas naloxone, a broad-spectrum opiate antagonist, moderately decreased light responsiveness. Because naloxone had no effect on these cell's directional tuning, the opiate system is probably not involved in the mechanism of directional sensitivity. Based on the effects of these transmitter candidates and their antagonists, a possible site fo DS subunits may be the ACh and GABA receptors on the membrane of DS ganglion cells. ACh provides light-evoked excitation that may, when potentiated by physostigmine, overcome asymmetric GABA inhibition. Although the role of glycine in directional sensitivity is small, it may be responsible for regulating presynaptic excitatory pathways leading to the DS ganglion cells.

Animals↗
PubMed1984

Temperature effects on the electroretinogram of the isolated carp retina.

The electroretinogram was recorded from the isolated retina of the carp while the temperature was varied systematically and while the preparation was under the influence of various pharmacological agents. In addition to the a-wave and the b-wave, the electroretinogram gave evidence of early and late oscillatory potentials. The procedures selectively modified the prominence of these and other less conspicuous components. A particularly significant finding was that some oscillatory potentials are largest at intermediate temperatures, but that they persist to very low ones. It is suggested that temperature control, variation of stimulus intensity, and the application of pharmacological agents may be combined to provide a useful method of separating retinal response components.

Animals↗
PubMed1983

Presynaptic uptake blockade hypothesis for LSD action at the lateral inhibitory synapse in Limulus.

We investigated the action of LSD at the putative indoleaminergic lateral inhibitory synapse in the lateral eye of Limulus polyphemus. We recorded extracellular and intracellular voltage responses from eccentric cells while producing inhibition either by light or by antidromic stimulation of the optic nerve in the presence of LSD, serotonin (5-HT), chlorimipramine, or a bathing medium whose high Mg++ and low Ca++ concentrations partially or completely blocked synaptic transmission. We found (a) light-evoked and antidromically stimulated lateral inhibition is enhanced during superfusion of low (1-5 microM) concentrations of LSD and suppressed by higher (5-20 microM) concentrations; (b) these actions of LSD are markedly reduced by bathing the retina in a medium high in Mg++ and low in Ca++; (c) very low concentrations of chlorimipramine, a putative uptake blocker of serotonin, appear to mimic actions of LSD both on eccentric cell firing rate and on lateral inhibition; (d) superfused 5-HT depresses lateral inhibition at all superthreshold concentrations (0.1-25 microM). These results suggest that LSD's action may require an intact inhibitory transmitter release and postsynaptic response mechanism, whereas serotonin exerts a direct postsynaptic effect. We propose that LSD blocks presynaptic uptake of transmitter at the lateral inhibitory synapse. The concentration dependence of LSD's action can be accounted for as follows: low concentrations partially restrict transmitter reuptake, thereby prolonging the lifetime of the transmitter in the synaptic cleft and thus increasing the magnitude and duration of postsynaptic inhibition. Higher concentrations cause more presynaptic uptake sites to be blocked; this causes accumulation of transmitter in the synaptic cleft, which causes a functional blockade of the synapse because of postsynaptic desensitization. As an alternative, we propose a hypothesis based on LSD action at presynaptic autoreceptors. Similar hypotheses can account for many aspects of LSD's action in mammalian brain.

Animals↗
PubMed1982

Inner plexiform circuits in the carp retina: effects of cholinergic agonists, GABA, and substance P on the ganglion cells.

Th effects on ganglion cell light responses and spontaneous activity of neurotransmitter candidates, applied by nebulizer spray and iontophoresis, were studied in the isolated carp retina. ACh, GABA, and substance P had strong effects on the ganglion cells; dopamine and the amino acids aspartate, glutamate, and glycine and only weak effects. ACh and substance P exerted their actions even when synaptic transmission was blocked by cobalt chloride, suggesting postsynaptic receptors for those agents on the ganglion cell membrane. The 3 amino acids and dopamine do not appear to act directly on the ganglion cells. The pharmacological sensitivity of ganglion cells was correlated with their physiological response type. About three-quarters of ON/OFF and half of other transiently responding ganglion cells were excited by micromolar concentrations of cholinergic agonists; most ON-center sustained ganglion cells were insensitive. The light response of some of the ACh-sensitive cells could be suppressed by cholinergic antagonists. Substance P generally excited ganglion cells with an ON-component in their light response. GABA inhibited cells of all response types, but affected least the OFF-center tonic cells. In view of these observations, and of corroborating histological evidence, we propose that ACh, GABA, and substance P are neurotransmitters that are released by amacrine cells and affect receptors located on ganglion cells.

Acetylcholine↗
PubMed1982

Acetylcholine and substance P: action via distinct receptors on carp retinal ganglion cells.

Substance P (SP), a neuropeptide, has been found in amacrine cells in a variety of vertebrate retinas. SP excited many of the ganglion cells we sampled in carp retina; many of these ganglion cells are directly excited by cholinergic agonists. It has been reported that SP modulates cholinergic synaptic transmission in some other neuronal systems by inhibiting or desensitizing cholinergic receptors. SP does not act in this way on the ganglion cell cholinergic receptors in isolated carp retina. Pulses of acetylcholine (ACh), applied to sensitive ganglion cells by microiontophoresis, were set to elicit consistent cellular responses. Application of SP to the retina through a nebulizing system (final concentration about 10(-6) M) did not reduce the excitation produced by the ACh pulse. In earlier work, we showed that the cholinergic receptors were nicotinic; in the present study, SP occasionally excited cells after the retina was treated with a nicotinic cholinergic antagonist, gallamine triethiodide. SP appears to excite cholinergic-sensitive ganglion cells at a postsynaptic site other than their nicotinic cholinergic receptor and via a pathway that does not require a presynaptic, SP-sensitive, ACh-releasing interneuron.

Acetylcholine↗