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Biomedical subjects

I Perlman

Publications and source records attributed to I Perlman.

71 records · Page 4Linked to original sources

The effects of background illumination on the photoresponses of red and green cones.

1. The photoresponses of light- and dark-adapted red and green cone photoreceptors were recorded intracellularly in the retina of the turtle, Pseduemys scripta elegans. Background illumination produced similar effects on both types of cones. 2. In response to the onset of a prolonged, steady background illumination the cone initially hyperpolarized to a peak which then sagged back to a steady-state polarization that was typically about one half the initial peak amplitude. This sag was observed for all backgrounds studied (dim as well as bright). 3. A resensitization was observed concomitantly with this sag; both the maximum increment and decrement responses grew in amplitude as light-adaptation proceeded. After about 2--3 min of background illumination, the amplitudes of these responses stabilized. 4. The dark-adapted cone produced graded responses to test pulses over a range of intensities spanning about 3.5 log units. The amplitudes of these responses were well fit by the relationship V = I.Vm/(I + sigma). 5. After 2--3 min of background illumination, 500 msec test pulses either brighter or dimmer than the background intensity were substituted for the background. The light-adapted intensity-response curves constructed from this data were similar to the dark-adapted curve but were shifted horizontally and slightly vertically, so that they still spanned about 3.5 log units of intensity. Thus, in the light-adapted cone, graded responses were elicited by a range of bright test pulses which would have produced saturated responses when delivered to the dark-adapted cone. 6. The 'off response' observed at the offset of the background became faster as the background intensity was increased. It also became faster with time following the onset of any particular background intensity. 7. It was concluded that cone sensitivity during any state of light-adaptation is determined by two mechanisms; response compression resulting from the instantaneous non-linearity between 'internal transmitter' concentration and membrane potential and a more active 'cellular adaptation' mechanism which is manifest as a shift in the intensity-response curve. In the steady-state condition of light-adaptation, most of the sensitivity changes are a result of the cellular adaptation mechanism. 8. Photopigment bleaching caused by the backgrounds, negative feed-back from horizontal cells and voltage dependent mechanisms in the cones could not account for this cellular adaptation. These effects of background illumination were interpreted in terms of the 'internal transmitter' hypothesis of phototransduction.

Adaptation, Ocular↗

Signal transmission from red cones to horizontal cells in the turtle retina.

1. Intracellular recordings were made from L-type horizontal cells in the retina of the turtle Pseudemys scripta elegans. The responses were evoked by 500 msec pulses of 'white' light. 2. L-type horizontal cells were classified as either, 'small receptive field' s.r.f. or 'large receptive field' l.r.f. based upon (1) receptive field size and (2) kinetics of responses to test flashes covering small and big spots. 3. Constant illumination of the entire receptive field, with any intensity studied, evoked a response that reached a peak and then slowly sagged back to a steady-state level that was about half the peak response. 4. Termination of backgrounds resulted in a very fast recovery of the membrane potential that overshot the dark-adapted potential. This 'off' response had faster kinetics in horizontal cells than in red cones. 5. The intensity-response curve measured around any background intensity was shifted along the log intensity axis toward higher test intensities. The curves obtained under light-adapted conditions were sharper than the curve measured in the dark-adapted state. 6. The photoresponses of red cones and s.r.f. horizontal cells were compared under similar states of adaptation. In the dark-adapted state of the gain, expressed as the millivolt change in the horizontal cell per millivolt change in the cone, was not linearly related to cone potential, and was highest for dim stimuli. Light-adaption modified the synaptic transmission to make the horizontal cells most sensitive to light modulation around the background illumination. 7. The mechanisms by which signal transmission can be modified by light-adaptation are discussed in terms of transmitter release by the presynaptic terminals and its binding to post-synaptic sites.

Adaptation, Ocular↗

Kinetics of bleaching and regeneration of rhodopsin in abnormal (RCS) and normal albino rats in vivo.

1. Rhodopsin concentration has been measured by the method of densitometry in retinae of rats with inherited retinal dystrophy (RCS) raised in darkness and compared with that of normal rats similarly reared. 2. In both RCS and normal rats the fraction of rhodopsin bleached is always directly proportional to the photon content of the light, I.t, where I is the light intensity in effective quanta (500 nm) cm-2 sec-1 and t is the duration of the bleaching exposure in seconds. 3. Rhodopsin photosensitivity for bleaching is slightly higher in RCS rats than in normals (2.3 (10)-16 cm2 chromophore-1 compared with 1.3 (10)-16 cm2 chromophore-1). 4. Rhodopsin regeneration in the dark in both RCS and normal rats cannot be described by the kinetics of a simple monomolecular chemical reaction. 5. Following 5 min bleaches, the regeneration rate becomes slower as the preceding bleach is made stronger. Regeneration in the dark is significantly faster in the RCS rats than in the normal ones. 6. In normal rats, after a full bleach, rhodopsin regenerates back to the dark-adapted level within 3--4 hr. In RCS rats rhodopsin regenerates to reach a plateau level, below the previous dark-adapted level, that lasts for several hours. 7. The faction of total rhodopsin that can regenerate gradually declines with age until in 70 days old RCS rats no rhodopsin regeneration can be measured by the ensitometer. However, total rhodopsin density (fully bleached-dark-adapted) is still close to normal.

Age Factors↗

Dark-adaptation in abnormal (RCS) rats studied electroretinographically.

1. Electroretinogram (e.r.g.) responses recorded from dark-reared rats with inherited retinal dystrophy (RCS) showed progressive decline in b-wave ampliture and prolongation of the time to the peak of the b-wave with age when compared with records obtained from dark-reared normal albino rats. 2. Dark-adaptation was followed in RCS and normal rats by recording the light intensity needed to evoke a criterion e.r.g. response at different time intervals after bleaching and 90% of the rhodopsin. 3. In normal rats, dark-adaptation was governed by two mechanisms. The first 25--35 min of recovery was determined by cones. The second branch, determined by the recovery of rods, lasted for about 3 hr and proceeded along an exponential time course with time constant of 41.4 +/- 2.4 min (S.E. of mean). 4. In RCS rats, the time course of the dark-adaptation after a 90% bleach depended on age. In 25--30 day old rats the recovery curve had at least three breaks separating three different mechanisms. Rats, 35--40 days old, exhibited double exponential recovery curves, while 45--70 day old rats recovered along a single exponential curve similar in time course to the cone branch of dark-adaptation found in normal rats. 5. Action spectra obtained from RCS rats at different time intervals of the recovery curve showed that in young rats, 25--30 days old, small e.r.g. responses recorded before bleaching and at the end of the recovery period were determined by rhodopsin while those recorded during the first part of the recovery from 90% bleach were determined by a combination of rods and cones. In RCS rats of advanced age (45--70 days old), rhodopsin was the major contributor to the e.r.g. responses recorded either before bleaching or at the end of the recovery period. 6. The gradual deterioration with age of the e.r.g. in RCS rats cannot be explained by either the decrease in quantum catch due to the decrease in rhodopsin content or by the linear relationship between log e.r.g. threshold and pigment concentration. 7. Using estimates of rhodopsin density within surviving rods obtained from retinal densitometry, it was shown that in RCS rats where more than 30% of normal levels of rhodopsin was located within the functioning rods, the log intensity needed for a criterion e.r.g. response measured at the end of the recovery period from a 90% bleach was linearly related to the fraction of 'functional' rhodopsin. 8. No simple relationship between log e.r.g. threshold and rhodopsin concentration could be found during the course of recovery in the dark from a strong bleaching exposure in RCS rats of all ages.

Age Factors↗

A long term follow up of ocular siderosis: quantitative assessment of the electroretinogram.

Siderosis oculi is a severe sequel of retained, iron made, intraocular foreign body. Iron atoms or ions, dissolved from the foreign body, may diffuse to the retina and produce irreversible cellular damage. Therefore, early extraction of an iron foreign body is recommended. When the risks of surgical intervention outweigh the danger of siderosis, the patient is periodically examined in order to detect the initial signs of siderosis. The most commonly used test for quantitative and objective assessment of retinal function is the electroretinogram (ERG). We report here a long term ERG follow-up (about 8 years) of a patient suffering from a unilateral iron intraocular foreign body. The development of siderosis was detected by any of the ERG responses; cone-dominated, rod-dominated or mixed cone-rod responses. However, the degree of the assessed damage varied and strongly depended upon the flash intensity used to elicit the ERG response and upon the ERG wave chosen to assess retinal function. The relationship between the ERG b- and a-waves showed a profound deterioration reflecting a reduction in signal transmission from the photoreceptors to the inner nuclear layer. These findings suggested that iron toxicity produced more damage to the inner retina than to the outer retina.

Electroretinography↗

Cone-rod dysfunction in patients with unexplained reduction in visual acuity.

Electrophysiologic tests were performed in 233 patients who complained of reduced visual acuity with no satisfactory clinical explanation. The functional integrity of the retina was assessed from the light- and dark-adapted electroretinogram. Macular function and conduction in the optic nerves were estimated from the flash visual evoked potentials. Of the 233 patients 78 were grouped together on the basis of the electrophysiologic and clinical findings. They were characterized by subnormal electroretinogram responses with the cone system more affected than the rod system. The flash visual evoked potential responses were of abnormal waveform and prolonged implicit times. Most of these patients exhibited normal fundi. The reduction in visual acuity, the degree of electroretinogram deficits and the pattern of the visual evoked potential responses were similar in both eyes of each patient, indicating a symmetric disorder. Slight deterioration of visual acuity and electrophysiologic variables were observed in 37 of the patients who were followed up over a period of up to 8 years. The electrophysiologic findings indicate that about 20% of patients complaining of unexplained reduction in visual acuity were suffering from a diffuse retinal disorder affecting the peripheral retina as well as the macular region. On the basis of electrophysiologic findings and clinical symptoms, we suggest grouping these patients under a new entity: cone-rod dysfunction.

Adaptation, Ocular↗

The action spectra of cone photoreceptors in the turtle (Mauremys caspica) retina.

Cone photoreceptors in the turtle retina are involved in intricate neuronal interactions with other retinal neurons that modify the responses of the cones to photons absorbed in their outer segments. Therefore, the action spectra of cones strongly depend upon the conditions of measurements. This study describes an attempt to derive the action spectra of turtle cones which are the least distorted by neuronal interactions. To achieve this goal, the photoresponses of cones and horizontal cells were recorded from the turtle retina under different conditions of adaptation using different patterns of the stimulating test flashes. The sensitivity action spectra, derived from small-amplitude (<1 mV) photoresponses, were strongly affected by the recording conditions indicating the contributions of multiple neuronal inputs. Action spectra, constructed from large criterion photoresponses, were less distorted by neuronal interactions and better described the spectral properties of the "isolated" cones. The action spectra of the hyperpolarizing inputs to chromaticity-type horizontal cells were derived by stimulating these cells with mixtures of a saturating red light and a monochromatic light of different wavelength and intensity. The action spectra were constructed from the intensity of the addend component needed to "pull down" the depolarizing response to the red component by a fixed criterion. These spectra, measured in red/green and yellow/blue C-type horizontal cells, are suggested to best represent the "isolated" M-cones and S-cones, respectively.

Absorption↗

Short-term effects of dopamine on photoreceptors, luminosity- and chromaticity-horizontal cells in the turtle retina.

The effects of dopamine on luminosity-type horizontal cells have been documented in different vertebrate retinas, both in vivo and in vitro. Some of these effects may reflect direct action of dopamine onto these cells, but indirect effects mediated by presynaptic neurons cannot be ruled out. Furthermore, direct effects of dopamine on horizontal cells may affect other, postsynaptic neurons in the outer plexiform layer. To test these possibilities, we studied the effects of dopamine on photoreceptors and all types of horizontal cells in the turtle (Pseudemys scripta elegans) retina. Receptive-field properties, responsiveness to light, and time course of light responses were monitored with intracellular recordings. Dopamine at a concentration of 40 microM exerted effects with two different time courses. "Short-term" effects were fully developed after 3 min of dopamine application and reversed within 30 min of washout of the drug. "Long-term" effects were fully developed after about 7-10 min and could not be washed out during the course of our experiments. Only the "short-term" effects were studied in detail in this paper. These were expressed in a reduction of the receptive-field size of all types of horizontal cells studied; L1 and L2 luminosity types as well as Red/Green and Yellow/Blue chromaticity types. The L1 horizontal cells did not exhibit signs of reduced responsiveness to light under dopamine, while in the L2 cells and the two types of chromaticity cells responsiveness decreased. None of the rods, long-wavelength-sensitive, or medium-wavelength-sensitive cones exhibited any apparent reduction in their receptive-field sizes or responsiveness to light. The present results suggest that the "short-term" effects of dopamine are not mediated by photoreceptors and are probably due to direct action of dopamine on horizontal cells.

Animals↗

NADPH diaphorase activity in mammalian retinas is modulated by the state of visual adaptation.

NADPH diaphorase histochemistry is commonly used to identify cells containing nitric oxide synthase (NOS), the enzyme catalyzing the production of nitric oxide from L-arginine. NADPH diaphorase activity and NOS immunostaining was demonstrated in different cells of the vertebrate retina; photoreceptors, horizontal cells, amacrine cells, ganglion cells, and Müller cells. However, the physiological role of nitric oxide (NO) in the retina has yet to be elucidated. In this study, we tested the assumption that NADPH diaphorase activity in the retinas of rabbits and rats depended on the state of visual adaptation. In the rabbit, light adaptation enhanced NADPH diaphorase activity in amacrine cells and practically eliminated it in horizontal cells. Dark adaptation induced the opposite effects; the NADPH diaphorase activity was reduced in amacrine cells and enhanced in horizontal cells. Retinas from eyes that were injected intravitreally with L-glutamate exhibited a pattern of NADPH diaphorase activity that was similar to that seen in dark-adapted retinas. In rats, the NADPH diaphorase activity of amacrine and horizontal cells exhibited adaptation dependency similar to that of the rabbit retina. But, the most pronounced effect of dark adaptation in the rat's retina was an enhancement of NADPH diaphorase activity in Müller cells, especially of the endfoot region. Assuming that NADPH diaphorase activity is a marker for NOS, these findings suggest that NO production in the mammalian retina is modulated by the level of ambient illumination and support the notion that NO plays a physiological role in the retina.

Adaptation, Ocular↗

Spectral properties of short-wavelength (blue) cones in the turtle retina.

Long- and medium-wavelength cones in the turtle retina participate in complex neural interactions. They are coupled via excitatory pathways to other cones and receive negative feedback inputs from luminosity-type horizontal cells. Little information has been collected on the S- (short-wavelength or blue) cones because they are scarce in the turtle retina and of smaller dimensions compared to the other cone types. In this paper, flash sensitivity action spectra and photoresponses of seven turtle S-cones were measured in the dark-adapted state and during chromatic background illuminations. The desensitizing action of monochromatic background lights was not uniform across the visible spectrum. A red background was most effective in desensitizing the S-cones to long-wavelength stimuli while a blue background light produced its strongest action on the photoresponses elicited by short-wavelength stimuli. The effects of chromatic adaptation on the S-cone action spectrum and on the kinetics of the small-amplitude photoresponses suggested that the S-cones in the turtle retina were involved in complex neural interactions. These included excitatory inputs probably originating in neighboring L-cones and inhibitory long-wavelength inputs probably mediated by L-type horizontal cells.

Absorption↗

Spatial-chromatic interactions in C-type horizontal cells of the turtle (Mauremys caspica) retina.

Horizontal cells are second-order retinal neurons that play a key role in spatial information processing. In some cold-blooded vertebrates such as turtles, a subtype of these cells, the chromaticity horizontal cells exhibit color-opponent responses and therefore are considered to be important also for color information processing. To reveal spatial and color interactions, the receptive-field properties of Red/Green and Yellow/Blue chromaticity horizontal cells in the retina of the turtle Mauremys caspica were studied by intracellular recordings from the everted eyecup preparation. We found that the polarity of the photoresponses depended not only upon the wavelength and intensity of the stimulus, but also upon its spatial configuration. Thus, a hyperpolarizing photoresponse that was elicited by full-field stimulation with bright light of wavelength close to the "neutral" one was reversed in polarity to a pure depolarizing one when a small spot or a thin annular pattern were used for stimulation. This finding could not be explained either by different balances between depolarizing and hyperpolarizing inputs to different cells or by stray light that effectively reduced the light intensity in the center of the small spot. Rather, it was found that the depolarizing and hyperpolarizing components were characterized by different receptive-field size and that these differences could account for the dependency of response polarity upon the spatial pattern of the stimulus. These findings indicate that color information processing in turtle C-type horizontal cells is a complex process that depends upon the wavelength and intensity of the light stimulus as well as upon its spatial properties.

Animals↗

Dynamic changes in the receptive fields of L1-type horizontal cells in the retina of the turtle Mauremys caspica.

The resistances of the horizontal cell syncytium in the vertebrate retina are modulated in a time-dependent fashion during light stimulation. Therefore, the spatial properties of horizontal cells are expected to change with time after the illumination conditions are altered. This study was designed to investigate time- and intensity-dependent changes in the receptive-field properties of L1-type horizontal cells in the turtle Mauremys caspica. Photoresponses were elicited by monochromatic (650 nm) light stimuli of 2-s duration covering retinal spots of different radii. The length constants were derived from the relationships between amplitude and spot radius that were constructed for different time intervals after onset of the light stimulus. For a given stimulus intensity, the length constant transiently increased to a peak value and then slowly recovered to a plateau level. When the length constant was compared to the amplitude of the response to full-field illumination for the entire duration of the light stimulus, an ellipse-like curve was obtained indicating that for a given membrane potential, two different values of the length constant could be obtained. Dopamine considerably reduced the size of the receptive fields but did not affect the time-dependent changes in the length constant. These results indicate that changes in the membrane resistance underlie short-term modulation of the receptive-field properties of turtle L1-type horizontal cells after onset of a light stimulus.

Animals↗

Neural interactions between cone photoreceptors and horizontal cells in the turtle (Mauremys caspica) retina.

Horizontal cells and cone photoreceptors in the vertebrate retina are interconnected by a complex network of synapses leading to the generation of color-coded responses in chromaticity horizontal cells. A simple cascade model of excitatory feedforward and inhibitory feedback synapses had been suggested to underlie these observations. In this study, the photoresponses of cones and horizontal cells were recorded intracellularly from the turtle eyecup. Three different approaches were adopted in order to test quantitatively the cascade model. Comparing linearity functions between these neurons indicated multiple excitatory inputs to each type of horizontal cells. The depolarizing photoresponses of R/G C-type horizontal cells were considerably faster than those of L-type horizontal cells but slower than those recorded from L-cones. This observation disagrees with the basic assumption of the cascade model that assign the depolarizing photoresponses of R/G C-type horizontal cells to a negative feedback pathway from L-type horizontal cells onto M-cones. Finally, the action spectra of each of the three types of horizontal cells could not be solely accounted for by input from one spectral type of cones. Only by assuming excitatory and inhibitory inputs from all spectral types of cones, the action spectra of all types of horizontal cells could be reconstructed. These findings suggest that the negative feedback pathways from horizontal cells onto cones in the turtle retina cannot solely account for the chromatic properties of the horizontal cells and support a direct inhibitory inputs from cones to turtle horizontal cells.

Animals↗

The role of potassium conductance in the generation of light responses in Müller cells of the turtle retina.

Müller cells are highly permeable to potassium ions and play a major role in maintaining potassium homeostasis in the vertebrate retina during light-evoked neuronal activity. Potassium fluxes across the Müller cell's membrane are believed to underlie the light-evoked responses of these cells. We studied the potassium currents of turtle Müller cells in the retinal slice and in dissociated cell preparations and their role in the genesis of the light-evoked responses of these cells. In either preparation, the I-V curve, measured under voltage-clamp conditions, consisted of inward and outward currents. A mixture of cesium ions, TEA, and 4-AP blocked the inward current but had no effect on the outward current. Extracellular cesium ions alone blocked the inward current but exerted no effect on the photoresponses. Extracellular barium ions blocked both inward and outward currents, induced substantial depolarization, and augmented the light-evoked responses, especially the OFF component. Exposing isolated Müller cells to a high potassium concentration did not cause any current or voltage responses when barium ions were present. In contrast, application of glutamate in the presence of barium ions induced a small inward current that was associated with a substantially augmented depolarizing wave relative to that observed under control conditions. This observation suggests a role for an electrogenic glutamate transporter in generating the OFF component of the turtle Müller cell photoresponse.

4-Aminopyridine↗

The contributions of voltage- and time-dependent potassium conductances to the electroretinogram in rabbits.

The electroretinogram (ERG) is generated by light-induced electrical activity in retinal cells. Since potassium ions and potassium conductances play a major role in determining the membrane potential of cells, changes in these are expected to affect the amplitude and pattern of the ERG. We recorded the ERG responses and the isolated P-III waves of rabbits after intraocular injections of specific blockers for potassium channels. 4-aminopyridine (4-AP) did not cause any noticeable changes in the ERG while tetraethylammonium chloride (TEA) induced time-dependent effects. Short-term (1-2 h) effects were expressed as significant augmentation of the b-wave with little change in the a-wave. At longer periods of follow-up, the a-wave increased in amplitude while the b-wave decreased. TEA augmented the amplitude of the isolated P-III wave. These effects of TEA can be explained by TEA-induced depolarization of the photoreceptors. Cesium ions and barium ions induced substantial augmentation of the b-wave. Barium but not cesium ions reduced the isolated P-III component of the ERG probably by blocking the potassium channels in the Müller cells. The augmentation of the b-wave by both barium or cesium ions is inconsistent with the Müller cells hypothesis for the ERG b-wave.

4-Aminopyridine↗

Turtle C-type horizontal cells act as push-pull devices.

Chromaticity (C-type) horizontal cells in the retina of cold-blooded vertebrates receive antagonistic inputs from cone photoreceptors of different spectral types leading to color opponency. The relative contribution of each spectral type of cones can be selectively altered by chromatic background illumination. Therefore, the spectral properties of C-type horizontal cells are expected to change when the intensity and color of ambient illumination are altered. In this study, we investigated the effects of chromatic background lights upon color opponency in Red/Green (RGH) and Yellow/Blue (YBH) C-type horizontal cells in the everted eyecup preparation of the turtle Mauremys caspica. Photoresponses were elicited by long-wavelength and short-wavelength light stimuli in the dark-adapted state and under conditions of chromatic background illumination. We found that the total voltage range. within which graded depolarizing and the hyperpolarizing photoresponses could be elicited, either increased or decreased depending upon the color of the background light. However, the maximal and minimal potential levels determined respectively by long-wavelength and short-wavelength light stimuli of supersaturating intensity remained unchanged, regardless of the wavelength and intensity of the background. These findings indicate that turtle C-type horizontal cells operate as push-pull devices. A sufficiently bright short-wavelength stimulus can push them all the way to the maximal hyperpolarizing level while a very bright long-wavelength stimulus can pull them towards the most depolarizing potential.

Adaptation, Ocular↗