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Biomedical subjects

I Perlman

Publications and source records attributed to I Perlman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Voltage- and time-dependent potassium conductances enhance the frequency response of horizontal cells in the turtle retina.

The contribution of voltage- and time-dependent potassium conductances to visual information processing in the distal turtle retina was studied in the isolated retina preparation. The effects of specific potassium channel blockers; tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the membrane potential and photoresponses of L-cones and L-type horizontal cells were monitored with intracellular microelectrodes. Both drugs produced a large depolarization of the L-type horizontal cells though the effect of 4-AP was more transient than that of TEA. While TEA produced response augmentation associated with negligible changes in the kinetics of the photoresponses, 4-AP induced profound changes in response kinetics which were seen as an overshoot of the resting potential at stimulus offset and a pronounced slowing down in the return of the membrane potential toward the prestimulus level. The effects of TEA on horizontal cells could be accounted for by the action of the drug on cone photoreceptors. The effects of 4-AP on the horizontal cells could not be attributed to an indirect action mediated by either the cone photoreceptors or by GABAergic and/or glycinergic neurons in the inner retina. These results suggest that voltage- and time-dependent potassium conductances act to speed up the recovery of the turtle horizontal cell membrane potential from the effects of bright light stimuli. Such a role was supported by the effects of potassium channel blockers on the frequency response curves of horizontal cells: the corner frequency was reduced on the average by 25%.

4-Aminopyridine↗
PubMed1993

Visual function in hypermetropia. An electroretinographic and psychophysical study.

Dark-adapted retinal function was tested electroretinographically and psychophsysically in patients with severe hypermetropia. These patients were first tested in 1982 and were classified into three electroretinographic categories subnormal, normal and supernormal, according to the amplitudes and the b-wave to a-wave relationships of their dark-adapted electroretinographic responses. These patients were invited for a follow-up examination to examine whether the subnormal electroretinogram represented a stationary or a progressive syndrome, to correlate functional vision to the electroretinographic findings and to determine the changes in refraction and electroretinographic responses that might have occurred during an 8-year period. No significant changes were seen in the amplitudes and b-wave to a-wave relationships of the electroretinographic responses. These observations supported the initial electroretinographic classification of the hypermetropic patients and indicated that the patients belonging to the subnormal group were probably characterized by a stationary defect. The psychophysically determined thresholds at different retinal loci (from 30 degrees nasal to 40 degrees temporal) were within the normal range for all the patients regardless of their electroretinographic characteristics. Thus, the abnormal electroretinographic responses of hypermetropic patients probably did not reflect abnormal retinal function but may be accounted for by changes in the electrical resistances of extraretinal tissues relative to that of the retina itself.

Adolescent↗
PubMed1993

Drug-induced retinal toxicity in albino rabbits: the effects of imipenem and aztreonam.

PURPOSE: To test the toxic action of two antibiotics, imipenem and aztreonam, on the functional and morphologic integrity of the albino rabbit retina. METHODS: Two commercial drugs were used--Tienam, which contains imipenem, and Azactam, which contains aztreonam. Different doses of these drugs were injected intravitreally. Retinal function was assessed from the electroretinogram (ERG) and the visual evoked potential (VEP). Retinal structure was examined at the light microscopic level. RESULTS: Imipenem did not affect the ERG and the VEP responses or the morphology of the retina up to a total injected dose of 0.98 mg (2 mg Tienam). Aztreonam was not toxic to the albino rabbit retina up to a total injected dose of 2.8 mg (5 mg of Azactam). Severe functional and morphologic retinal damage was seen when 10 mg of Azactam was injected. A similar degree of damage was seen when a dose of 5 mg L-arginine, an ingredient of Azactam, was injected into the vitreous. CONCLUSIONS: Imipenem and aztreonam are nontoxic to the albino rabbit retina at concentrations that are 500-fold higher than their effective dose against bacterial infection. Azactam is highly toxic at high levels (more than 10 mg injected into the vitreous). Most of the toxicity could be explained by the L-arginine content of the drug.

Animals↗
PubMed1993

The effects of myristyl gamma-picolinium chloride on the rabbit retina: morphologic observations.

PURPOSE: This study was designed to localize the site of action of myristyl gamma-picolinium chloride (MGP) in the rabbit retina and to evaluate the extent of the structural damage induced by the drug. METHODS: The structural damage was assessed at the light microscopic level in eyes treated with various concentrations of MGP at different time intervals after intravitreal injection of the drug. Glial fibrillary acidic protein (GFAP) immunoreactivity was tested in the same eyes and served as an index of retinal damage. RESULTS: The rabbit retinas, examined about 1 mo after MGP injection, exhibited loss of photoreceptors and thinning of the retina in the regions close to the site of injection; remote retinal areas appeared morphologically intact or only slightly affected. Immunocytochemical analysis demonstrated the presence of GFAP in Müller (glial) cells throughout the entire retina. When the effects of MGP were examined at short time intervals (24 and 72 hr) after injection, severe morphologic damage in areas adjacent to the site of drug injection developed in parallel with the electroretinographic findings. However, GFAP could not be demonstrated. CONCLUSIONS: MGP, the preservative used in Depo-Medrol (Upjohn, Kalamazoo, MI), is highly toxic to the rabbit retina.

Animals↗
PubMed1992

Relationships between the electroretinogram a-wave, b-wave and oscillatory potentials and their application to clinical diagnosis.

The electroretinogram is the electrical response of the retina to a light stimulus. The amplitude and temporal pattern of its components, the a-wave, the b-wave and the oscillatory potentials, depend on the functional integrity of the retina, on the intensity of test flash reaching the retina and on the ambient illumination. The latter contributions to the normal variability in the electroretinogram can be circumvented by constructing the relationships between the different electroretinogram waves. The electroretinogram responses were recorded from 18 dark-adapted subjects with normal vision. The slope of the a-wave and the amplitude of the b-waves were measured in the time domain. The oscillatory potentials were isolated by a digital filter and were transformed to the frequency domain for quantitative measurement. The relationship between each pair of variables could be fitted by linear segments. Our findings suggest that this mode of electroretinogram analysis can be useful in localizing the site of action of retinal disorders and that the relationship between the a-wave slope and the power density of the oscillatory potentials is a useful index for identifying disorders of the inner retina.

Adult↗
PubMed1991

The effects of Depo-Medrol preservative on the rabbit visual system.

Periocular injections of corticosteroids play an important role in the management of various ophthalmologic diseases. The Depo-Medrol vehicle, injected into the vitreous, was shown to be toxic to the lens and to the retina when applied at double strength. The authors examined the effects of Depo-Medrol and one of the components of its vehicle, myristyl-gamma-picolinium chloride (MGP), on the functional integrity of the rabbit visual system. Visual function was assessed objectively from the electroretinogram (ERG) and the visual evoked potential (VEP). The experimental drugs were injected into the vitreous humor of one eye while saline was injected into the fellow eye for control. Depo-Medrol did not produce any measurable effects on the ERG or the VEP. When MGP solutions were injected in concentrations at least twice as large as that in the Depo-Medrol, significant reductions in the light- and dark-adapted ERG responses were seen. The effects of the drug on the ERG responses was seen as early as 3 days postinjection and developed to its maximal level within 1-2 weeks. No ERG recovery was seen over a period of more than 2 months. The VEP, elicited by applying light stimuli to the experimental eye, was characterized by low amplitude and delayed implicit time compared with the response obtained from the control eye.

Animals↗
PubMed1990

The effects of GABA and related drugs on horizontal cells in the isolated turtle retina.

The role of GABA in the outer plexiform layer of the turtle retina has been examined by intracellular recordings from L- and C-type horizontal cells in the isolated retina preparation. GABA (1-5 mM) slightly depolarized the L-type horizontal cells, reduced the amplitude of their photoresponses, and slowed down the rate of hyperpolarization during the ON component of the photoresponse. These effects could not be replicated by either muscimol or baclofen. When synaptic transmission from the photoreceptors had been blocked by either kynurenic acid or cobalt ions, GABA depolarized L-type horizontal cells and augmented the remaining photoresponses. Neither muscimol nor baclofen exerted any effect on L-type horizontal cells under these conditions. Nipecotic acid, a competitive inhibitor of the GABA-uptake system, induced effects on turtle L-type horizontal cells which were similar to those exerted by GABA. Thus, the complex GABA effect on turtle L-type horizontal cells seems to represent the summation of at least two actions; an indirect one mediated by the red cones via GABAa-type receptors and a direct one which probably reflects the activation of an electrogenic GABA-uptake system. GABA (1-5 mM) induced a transient depolarization in C-type horizontal cells but eliminated color opponency in only three cells out of seven studied. This observation is inconsistent with the notion that the only neural mechanism responsible for the chromatic properties of C-type horizontal cells in the turtle retina is a GABAergic negative feedback from the L-type horizontal cells onto the green ones.

Animals↗
PubMed1990

Effects of calcium ions on L-type horizontal cells in the isolated turtle retina.

A technique by which the retina can be isolated from the turtle eye is described. Scanning electron microscopy revealed morphological variability between preparations and also between regions of the same one. Large areas were often totally free of any pigment epithelial cells, yet contained a high proportion of photoreceptors with complete outer segments. However, adjacent regions may contain photoreceptors without outer segments or with fragmented ones. The physiological properties of the horizontal cells also demonstrated large variability between different preparations. In all cases, lowering calcium concentration from 2 mM to 0.1-0.5 mM depolarized the horizontal cells and augmented the amplitude of the maximum photoresponses. However, these effects were accompanied by changes in the photoresponse kinetics and by a reduction in the horizontal cell sensitivity to light. Moreover, prolonged exposure to low calcium induced permanent damage to the retina as was indicated by the reduction in the response amplitude after superfusion with 2 mM calcium solution had been resumed. The toxic effects of low calcium were most apparent when superfusion with 0.1-1.0 microM calcium concentration was performed. These solutions induced complex time-dependent effects on the resting potential of horizontal cells and on the amplitude and kinetics of the photoresponses. We conclude from these observations that the normal concentration of extracellular calcium in the turtle retina is in the 2 mM range.

Animals↗
PubMed1990

Background and bleaching adaptation in luminosity type horizontal cells in the isolated turtle retina.

1. The effects of background illumination and bleached photopigment on luminosity type horizontal cells were studied in the isolated turtle retina. 2. Background illumination, which produced less than 60% bleaching, hyperpolarized and desensitized the horizontal cells to a degree which depended upon the background intensity. The desensitization of horizontal cells by these backgrounds is described by a Weber-Fechner type relationship. This desensitization primarily reflects the activation of a 'gain reduction' mechanism and cannot be accounted for by 'response compression'. 3. Following the termination of these backgrounds, horizontal cell sensitivity partially recovered but did not return to the pre-background, dark-adapted level. This desensitization was attributed to the presence of bleached photoproducts which were produced by the background exposure. 4. Application of very bright backgrounds caused the horizontal cells to initially hyperpolarize, and then to gradually depolarize towards the dark-adapted level along an exponential time course which appeared to reflect the decreased quantal catching associated with very high levels of photopigment bleaching. 5. From the time constant of the exponential decay of horizontal cell potential during the bright background illumination, the photosensitivity to bleaching of the cone photopigment was determined to be 4.5 x 10(7) effective quanta (633 nm) microns-2. 6. After termination of bright backgrounds which bleached more than 99% of the cone photopigment, the horizontal cell sensitivity increased linearly with time and after 25 min reached a level which was about 15% of the pre-background sensitivity. 7. Bleached photopigment reduces light sensitivity via at least two different mechanisms. For moderate degrees of bleaching (less than 95%), the presence of bleached photoproducts plays the major role in sensitivity control, producing a desensitization which is logarithmically related to the fraction of bleached pigment. During extensive bleaching (greater than 99%), the contribution of reduced quantal catching to sensitivity control becomes apparent and produces an additional loss in sensitivity which is linearly related to the fraction of unbleached pigment present.

Adaptation, Ocular↗
PubMed1989

Responses of isolated white perch horizontal cells to changes in the concentration of photoreceptor transmitter agonists.

Current and voltage responses elicited by increasing or decreasing the concentration of L-glutamate or its analog kainate around isolated cone horizontal cells were measured with patch pipettes using the whole cell recording configuration. Application of these photoreceptor transmitter agonists induced inward currents in voltage-clamp experiments (for negative holding potentials) and depolarizing responses in current-clamp experiments. Continuous exposure to either drug produced inward currents which were maintained for as long as superfusion with the drugs continued. Reducing the concentration of the agonists by pressure ejection of pulses of drug-free Ringer's solution onto the cells completely turned off the drug-induced currents. Under current-clamp conditions, pulses of control Ringer's elicited hyperpolarizing responses of large amplitude (40-80 mV). The data demonstrate the ability to simulate in vitro the horizontal cell's photoresponses and thus support the use of cultured cells as a model system for studying horizontal cell physiology and pharmacology.

Animals↗
PubMed1988

Modulation of cone-to-horizontal-cell signal transmission in the turtle retina by magnesium ions.

The modulation by magnesium ions of cone-to-horizontal-cell signal transmission was studied in the turtle superfused everted eye-cup preparation using solutions which contained various concentrations of divalent cations and/or chelating agents (EDTA and EGTA). Removal of magnesium ions from 'normal' solutions had no apparent effect on the horizontal cells provided that 'normal' levels of calcium ions were maintained. Solutions which actively removed calcium but contained 'normal' levels of magnesium hyperpolarized horizontal cells, reduced the amplitude of their photoresponses but also changed the character of these photoresponses; dim stimuli evoked purely depolarizing responses while bright flashes elicited triphasic responses. Active removal of both calcium and magnesium from the superfusate and from retinal stores with chelators depolarized the horizontal cell and eliminated light-evoked responses. These solutions also depolarized the cones but augmented their light-evoked responses. We conclude that magnesium ions can modulate the membrane potential of horizontal cells, but this role can be revealed only in the absence of calcium ions. Further, the depolarizing responses seen in low calcium, 'normal' magnesium superfusion indicate that the ionic mechanisms underlying the horizontal cell photoresponse are more complex than has been previously described.

Animals↗
PubMed1988

Neural organization of the retina of the turtle Mauremys caspica: a light microscope and Golgi study.

The organization of the retina of the turtle species Mauremys caspica, found in fresh water ponds of Israel, has been examined by light microscopical techniques including examination of fresh wholemount retina, one micron blue-stained vertical sections and Golgi-stained material. The anatomical findings on Mauremys retina have been compared with those of the Pseudemys retina (Kolb, 1982) which is more commonly used for electrophysiological and neurochemical studies in the USA. The photoreceptors of Mauremys are similar in type and oil droplet content to Pseudemys photoreceptors except for the double cone in Mauremys. This cone type appears more abundant than in Pseudemys and the principal member contains a yellow oil droplet instead of an orange oil droplet. Golgi staining reveals that the cell types that have been seen in Pseudemys are found in Mauremys with identical morphology. In addition, two amacrine cell types that were not before described for Pseudemys have been added to the classification. One of these is the tristratified dopaminergic amacrine cell described in immunocytochemical studies (Witkovsky et al., 1984; Nguyen-Legros et al., 1985; Kolb et al., 1987). We have used these anatomical studies on Pseudemys and Mauremys retina to form a catalogue of neural types for the turtle retina in general. We conclude with an attempt to combine findings from anatomy, electrophysiology, and neurochemistry to form an overview of the organization of this reptilian retina.

Animals↗
PubMed1988

Local superfusion modifies the inward rectifying potassium conductance of isolated retinal horizontal cells.

1. Horizontal cells were enzymatically and mechanically dissociated from the white perch (Roccus americana) retina and voltage clamped using patch electrodes. Steady-state current-voltage (I-V) relationships of solitary horizontal cells were determined by changing the membrane potential in a rampwise fashion. 2. The I-V curve of cells bathed in normal Ringer solution exhibited a large conductance increase at negative membrane potentials. This conductance activated near the K+ equilibrium potential, had no clear reversal potential, was enhanced by raising the extracellular concentration of K+, and was suppressed by external Cs+. These properties identify the conductance as the inward (anomalous) rectifier. 3. Continuous superfusion of the cells' local environment with drug-free Ringer reduced the magnitude of the inward rectifier current and shifted its activation point to more negative potentials. This effect developed over approximately 30 s, lasted as long as superfusion continued and was reversible upon cessation of superfusion. 4. Pressure ejection of drug-free Ringer solution onto cells bathed in the identical solution also reduced the magnitude of the inward rectifier current, although the effects were more rapid and more transient than those exerted by superfusion. Pressure ejection had little effect when cells were simultaneously superfused with Ringer, suggesting a common mode of action on the inward rectifier. 5. In the absence of superfusion, pressure ejection of Ringer containing 200 microM L-glutamate had a biphasic effect on membrane conductance. At potentials above -60 mV, glutamate caused a conductance increase with a reversal potential near +10 mV. At potentials below -60 mV, glutamate caused a conductance decrease whose reversal potential could not reliably be determined. The latter effect was similar to the suppression of the inward rectifier by application of Ringer alone, suggesting that it may represent an artifact of pressure ejection rather than a direct effect of glutamate. 6. In support of this interpretation, we found that pressure ejection of glutamate in the presence of external Cs+ (which blocks the inward rectifier) or during local superfusion with Ringer (which prevents attenuation of the inward rectifier by pressure ejection) did not cause a conductance decrease at negative potentials. Under these conditions, glutamate caused primarily a conductance increase with a reversal potential near +10 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Light adaptation of red cones and L1-horizontal cells in the turtle retina: effect of the background spatial pattern.

Electrical coupling allow red cones and L1-horizontal cells to respond to light stimuli illuminating remote retinal loci. The contribution of the spatial pattern of background light to flash sensitivity of red cones and L1-horizontal cells was studied intracellularly in the turtle retina. Lateral spread of background adaptation was observed in the cones. The sensitivity of the cones was related to the steady hyperpolarization of the cells irrespective of the background's spatial pattern. Light sensitivity of L1-horizontal cells mainly depended upon the background illuminating their dendritic field. Unlike red cones, the horizontal cells responded differently to spot and annular backgrounds regardless of the steady hyperpolarization induced.

Adaptation, Ocular↗
PubMed1987

The effects of prolonged superfusions with acidic amino acids and their agonists on field potentials and horizontal cell photoresponses in the turtle retina.

The effects of prolonged superfusions with acidic amino acids and their agonists, kainic acid (KA) and N-methyl-D-aspartate (NMDA), on horizontal cells, and extracellular field potentials were studied in the turtle everted eyecup preparation using simultaneous intracellular and extracellular recordings. In a fresh preparation initial superfusions with each of the above agents usually induced a large (up to 60 mV) transient negative extracellular field potential recorded adjacent to horizontal cells, followed by a sustained negative potential of lesser amplitude (up to 10 mV). The amplitude of the sustained potential did not vary with subsequent superfusions, whereas that of the transient phase was reduced. KA and NMDA were much more potent (at least 300 times) in evoking these field potentials than either acidic amino acid. The horizontal cell transmembrane potential was monitored as the difference between the intra- and extracellular potentials. Superfusion with KA and NMDA produced a triphasic time course of the drug effect consisting of an initial depolarization with reduced photoresponses, a rehyperpolarization of the membrane accompanied by a growth of the light responses followed by a gradual depolarization and loss of photoresponses. Superfusion with the acidic amino acids usually produced a biphasic response that resembled qualitatively the first two phases of the response to KA and NMDA. This biphasic response was occasionally followed by a gradual depolarization and loss of the light response. The kinetics of the transient component of the field potential and the rapid reduction and regrowth of the photoresponses recorded during superfusion with these agents suggests an initial action of these drugs, which is of a nonsynaptic origin and which may be an expression of a drug-induced spreading depression. The kinetics of the photoresponses recorded during superfusion with KA, L-aspartate, and L-glutamate were similar but differed from those recorded during superfusion with NMDA. The difference in the effects of NMDA and KA on photoresponse kinetics suggests that two types of acidic amino acid receptors may be present in the outer plexiform layer of the turtle retina.

Animals↗
PubMed1987

Recovery of the electroretinogram in rabbits after argon laser photocoagulation.

Argon laser is widely used to coagulate the diabetic retina in order to inhibit the proliferative stage of diabetic retinopathy. Ten pigmented rabbits underwent retinal photocoagulation with argon laser. Retinal function was assessed electroretinographically before treatment and at different time intervals after treatment. The ERG responses measured 4-7 days after treatment were reduced in amplitude by a degree which was proportional to the number of laser applications. In five eyes that were treated with at least 1000 applications the ERG responses were very small when measured 4 days post-treatment. However, a gradual recovery was observed and within 2 months the ERG responses approached the normal pretreatment amplitudes. Histological findings from light and electron-microscopy suggested that the ERG recovery could not be solely explained by healing of the coagulated areas. Structural differences were seen in the pigment epithelial layer between a retina obtained immediately after treatment and one studied after ERG recovery. It is suggested that changes in the electrical resistance of the pigment epithelium may contribute to the ERG reduction seen immediately after laser treatment in the rabbit and to the increase in the ERG amplitude observed during the apparent functional recovery of the retina.

Animals↗
PubMed1986

The effects of continuous superfusion of L-aspartate and L-glutamate on horizontal cells of the turtle retina.

We have studied the effects of prolonged superfusion with L-aspartate and L-glutamate on the membrane potential and photoresponses recorded in luminosity type horizontal cells in the turtle retina using an everted eyecup preparation. These acidic amino acids produce effects which are a function of the past history of the impaled cell. Initial prolonged superfusions with 30 mM of either drug has no pronounced effect on the membrane potential and photoresponses of horizontal cells. Subsequent superfusions with either agent eventually produce depolarizations with reductions in the amplitudes of the light evoked responses. These effects, however, are transient; the horizontal cell rehyperpolarizes and the light evoked response grows with time. In a retina which had been stored at 4 degrees centrigrade for 20 hours, an initial superfusion with L-aspartate solution produced an immediate depolarization of the horizontal cell and complete suppression of the light evoked response for as long as the amino acid was present. The data are consistent with the existence of powerful amino acid uptake mechanisms operating at a number of sites within the inner and outer retina but also raise questions about the role of acidic amino acids in the outer plexiform layer of the turtle retina.

Animals↗