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K Kohler

Publications and source records attributed to K Kohler.

At least 55 records · Page 3Linked to original sources
PubMed1995

The renin-angiotensin system--a possible neuromodulator in the human retina?

Morphology studies imply a possible contribution of the renin-angiotensin system (RAS) to neurotransmission in the mammalian retina. To investigate further the functional role of the RAS in the visual system of humans, we tested the effects of the angiotensin-converting enzyme (ACE) inhibitor Captopril (Capt; 25 mg) on electroretinogram (ERG) recordings, the cone flicker threshold (CFT), the FM-28-HUE test, and the psychophysical rod threshold in healthy volunteers. The parameters of renin, angiotensin, and blood pressure were controlled. We obtained the following results. First, Capt induced a significant decrease in amplitudes of the scotopic b-wave, oscillatory potentials, and the a-wave. The latency of responses to 30-Hz flicker was increased. Second, the CFT was reduced to a lower intensity, whereas the final rod threshold remained unchanged. These results are in accordance with previous immunocytochemical and electrophysiological data. They cannot be explained exclusively by the observed changes in systemic blood pressure. We conclude that the RAS may possibly be involved in retinal neurotransmission in humans in addition to its vascular effects.

Administration, Oral↗
PubMed1995

Ethambutol alters spinule-type synaptic connections and induces morphologic alterations in the cone pedicles of the fish retina.

PURPOSE: Ethambutol can cause optic neuropathy and deficiencies in color-opponent visual processing in patients treated for tuberculosis. In fish, Ethambutol induces color vision deficiencies similar to those observed in humans and affects color coding in retinal ganglion cells. Color opponency in fish is mainly mediated by a horizontal cell feedback onto cones thought to be provided by spinules. The authors examined whether Ethambutol affects spinules and is, therefore, able to alter color processing at a distal stage, that is, at the first synaptic connection within the retina. METHODS: Ethambutol was injected into the vitreous of either dark- or light-adapted fish. After drug application, fish were held under different illumination conditions. Thereafter, the retinas were dissected and prepared for electron microscopy. Ultrathin tangential sections of retinas were examined at the level of the outer plexiform layer. RESULTS: In already light-adapted retinas, a high dose of Ethambutol (10 mM) reduced the number of spinules by 30%. Ethambutol application in the dark with subsequent light adaptation resulted in severe dose-related inhibition of light-induced spinule formation. In these experiments, low doses (0.1 mM) of Ethambutol caused 40% inhibition, and high doses (10 mM) caused 70% inhibition. Besides affecting spinules, Ethambutol occasionally induced a degeneration of cone pedicles. This neurotoxicity only occurred in cones exposed to light. CONCLUSIONS: Results show that Ethambutol alters synaptic connections between horizontal cells and cones in a dose-related fashion; Ethambutol treatment can be toxic for cone pedicles and can cause their degeneration; and the rod pathway is not affected by the drug. This indicates that Ethambutol influences the color-coding process already at the level of the cone-horizontal cell synapse.

Animals↗
PubMed1994

Persistent increases in scotopic B-wave amplitudes after lead exposure in monkeys.

The electroretinogram (ERG) of rhesus monkeys was re-examined more than 2 years after termination of lead exposure when mean blood lead levels had declined to values below 10 micrograms dl-1. Amplitude of the b-wave was increased by lead exposure at scotopic conditions, while there were no changes in photopic signals. The lead-induced effects were similar to alterations detected during the treatment phase and, thus, are not dependent on current exposure. Taking into account, that dopamine antagonists cause similar changes in the ERG, it is suggested that the observed effects may be mediated by a permanent change of dopaminergic processes since immunoreactivity also revealed adverse effects on the dopaminergic system in the retinae of these monkeys.

Animals↗
PubMed1994

6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia.

Degradation of the retinal image by translucent occluders during postnatal development induces axial myopia in chickens, tree shrews and monkeys. Local visual deprivation produces myopia even in local regions of the eye and neither accommodation nor intact connection between the eye and the brain are necessary. Therefore, it is an important question whether a similar local-retinal pathway translating visual information into growth or stretch signals to the underlying sclera is acting to emmetropize the growing eye. It is not known until now whether occluder deprivation triggers similar eye growth (or scleral stretch) mechanisms that are also responsible for visual guidance of normal refractive development. We here report that, in chickens, 6-hydroxy dopamine suppresses deprivation-induced myopia but has no effect on the magnitude of changes in axial eye elongation that are induced by spectacle lenses. The result suggests that, in chickens with normal accommodation, two pharmacologically different feedback loops may be responsible for deprivation myopia and lens-induced refractive errors.

Animals↗
PubMed1994

[Experimental studies of the significance of the renin-angiotensin system in the retina. A review].

BACKGROUND Many peptides now identified in the brain were previously thought of as exclusively peripheral hormones. Among those, the renin-angiotensin system (RAS) is not only found to be of great importance in peripheral vasomotor and electrolyte homeostasis but also acts as neurotransmitter or modulator in the central nervous system. Here we review a number of experiments performed by us pointing to a modulation effect of the RAS unrelated to its vasoactive mechanisms. The biochemical basis as well as the different methods employed will be described in detail. METHODS RAS enzyme activity within the different ocular structures were determined by means of fluorimetric measurements. Possible neurophysiological effects of the RAS on retinal function were established through electroretinographic in-vitro and in-vivo recordings. Immunocytochemical staining was employed to morphologically identify possible sites involved. RESULTS The performed fluorimetric measurements revealed highest Angiotensin-Converting Enzyme (ACE) activity within the neuroretina. Electroretinographic experiments have shown that variation in angiotensin-II activity is followed by reversible, dose-dependent effects on inner retinal signals. Clear evidence was found by immunohistochemistry that there is a discrete subpopulation of angiotensin-positive cells in the inner retina. CONCLUSIONS These findings demonstrate that the Renin-Angiotensin-System has neuronal sources and is physiologically active in the mammalian retina not purely related to vasoactive mechanisms. The RAS effector hormone angiotensin-II might therefore be a putative neurotransmitter in a subpopulation of retinal neurons. Reported side-effects of vasoactive substances, such as ACE-inhibitors on the visual function might be explained hereby.

Animals↗
PubMed1994

Angiotensin II-like immunoreactivity in the retina of some mammalian species.

The decapeptide angiotensin II (AngII) is a circulating hormone and the most important endogenous vasoconstrictor. In the central nervous system (CNS), AngII has been reported to have a transmitter-like function. In the retina angiotensin I (AngI), the precursor protein of AngII, and AngI-converting enzyme (ACE), the rate-limiting enzyme for AngII synthesis, are present. Both ACE inhibition and application of an AngII antagonist affect the b-wave of the electroretinogram. In the present study we used immunocytochemical techniques to identify putative AngII-containing cells in the bovine, cat, and rabbit retina. In the rabbit retina, faintly labeled amacrine cells were visible at the inner border of the inner nuclear layer. Preincubation with protease inhibitors (PI) resulted in an enhanced immunoreaction and in the labeling of ganglion cells and fibers in the inner plexiform layer. In the bovine retina, AngII-like immunoreactivity was detectable only after preincubation with PI. Under these conditions, ganglion cells and amacrine cells as well as cells in more distal parts of the inner nuclear layer were stained. In the cat retina, AngII-like immunoreactivity was detectable only after preincubation with PI and exogenous AngII. Photoreceptor and ganglion cells showed an enhanced AngII-like immunoreaction, and amacrine cells were stained preferably in clusters that were irregularly distributed within the retina. Our results demonstrate that AngII is a putative neurotransmitter in a subpopulation of mammalian amacrine cells.

Angiotensin II↗
PubMed1993

Spinule formulation in the fish retina: is there an involvement of actin and tubulin? An electronmicroscopic immunogold study.

During light-adaptation dendrites of teleost horizontal cells form finger-like processes, called 'spinules', which are characterized by synaptic membrane densities. To investigate the involvement of cytoskeletal elements in the formation and retraction of spinules, effects of the microtubule and actin inhibitors colchicine and cytochalasin D were examined by injection into the vitreous. Both substances inhibited the light-induced spinule formation. The ultrastructural immunolocalization of tubulin revealed labelling of dendrites only in their proximal parts. The distal parts of dendrites which invaginate into cone pedicles were free of label. Treatment with anti-actin revealed immunoreactivity along the entire length of dendrites up to the dendritic terminals. The spinules, however, showed no labelling. This finding does not support the hypothesis that spinules are protruded by actin polymerization. After cytochalasin D treatment the density of label in the dendritic terminals was enhanced by a factor of three, which suggests an accumulation of actin. Thus, spinule inhibition by cytochalasin D is probably caused by distortion of a functional actin network in the dendritic terminals.

Actins↗
PubMed1993

[Immunohistochemical studies of the role of dopaminergic retinal cells in neuronal light adaptation].

BACKGROUND: Tyrosine hydroxylase (TH) like immunoreactivity was investigated in frozen sections and in whole mounts of the chicken and bovine retina in order to investigate the distribution and role of dopaminergic structures in retinal circuiting. METHODS: By means of monoclonal antibodies against tyrosine hydroxylase the dopaminergic retinal structures were marked and their distribution determined by light microscopy. RESULTS: In both species TH-positive labelled cell bodies were localized in the innermost part of the inner nuclear layer (INL) close to the inner plexiform layer (IPL). In addition, in bovine retina TH-positive cell bodies were also located in the IPL and in the ganglion cell layer. TH-positive cell bodies gave rise to one to four fibers, which extended into sublayer 1 of the inner plexiform layer. In this sublayer fine fibers with button like structures were visible establishing a dense TH-positive plexus. In both species within this plexus small spots, free of any staining and surrounded by a ring of TH-positive fibers, could be observed. These "ring-like" structures were twice as frequent in bovine than in chicken retina. One to three thicker fibers per cell project into sublayer 3 and 4-5 of the IPL. In sublayer 3 of chicken retina they ramified into very long and fine fibers with small "bouton" like knobs. In bovine retina similar long fine fibers are found predominantly in sublayer 4-5. In sublayer 4-5 of the chicken retina the fibers were short and thick and shows a clear ramification pattern. They were found to be in close contact to the fibers of adjacent TH-positive cells. In bovine retina thin fibers arose from the TH-positive plexus in sublayer 1, passed through the INL and ramified within the outer plexiform layer (OPL). In chicken retina fibers only occasionally entered the INL; in the OPL fibers never could be observed. The appearance of TH-positive cells in the bovine and chicken retina resembles that of TH-positive cells found in other vertebrates. In whole mounted retinae from chicken and bovine the mean-density of TH-positive cells was 23 cells/mm2 and 27 cells/mm2, respectively. CONCLUSIONS: The fact that in the rod dominated bovine retina dopaminergic "ring-like" structures are observed more frequently than in the chicken retina may give a morphological hint that dopaminergic amacrine cells might be involved in neuronal retinal light adaptation.

Adaptation, Ocular↗
PubMed1992

Dose-dependent effects of 6-hydroxy dopamine on deprivation myopia, electroretinograms, and dopaminergic amacrine cells in chickens.

We found that a single intravitreal injection of 6-hydroxy dopamine (6-OHDA) is highly efficient in blocking the development of deprivation-induced myopia in young chickens. To investigate the effects of 6-OHDA on retinal function, we studied electroretinograms (ERGs) in chickens aged 15-25 days, 4 days subsequent to the injection. Both spectral sensitivity and oscillatory potentials were tested. In addition, a histological examination was performed of dopaminergic amacrine cells labeled by a monoclonal antibody against tyrosine hydroxylase. We found that, at doses of 6-OHDA sufficient to suppress deprivation myopia entirely, no effect could be detected on either the ERGs or on the density and appearance of dopaminergic amacrine cells. For higher doses, spectral sensitivity and the number of dopaminergic amacrine cells declined gradually. In contrast, as doses increased, oscillatory potentials 1 and 2 grew in amplitude only to decline at the highest doses. The results indicate that (1) development of deprivation myopia requires normal retinal function and that (2) slight changes in the gains of dopaminergic pathways are sufficient to block the development of deprivation myopia.

Animals↗
PubMed1991

Protein kinase C mediates transient spinule-type neurite outgrowth in the retina during light adaptation.

Light and dark adaptation of the teleost retina is accompanied by a remarkable morphological rearrangement of the synaptic connections between photoreceptors and second-order neurons: during light adaptation, numerous new neurites, the so-called spinules, arise from the terminal dendrites of horizontal cells invaginating the cone pedicle, and during dark adaptation, these spinules are retracted. The formation of these spinules is paralleled by the appearance of color opponency in horizontal and ganglion cells, which led to the suggestion that these spinules are the site of the inhibitory synapses in the negative feedback loop between cones and horizontal cells. The formation of the spinules in the light and their disappearance in darkness have a time course of minutes and are modulated by the neurotransmitters dopamine and glutamate, respectively. Neurotransmitters can modulate neuronal processing through a variety of second messengers that activate protein kinases, resulting most commonly in protein phosphorylation. Herein we report that activation of protein kinase C by phorbol esters promotes the formation of new horizontal-cell spinules in animals kept in the dark. Partial inhibition of protein kinase C activation with sphingosines prevents the formation of new spinules during light adaptation but does not affect established spinules. The spinule-forming effect of phorbol esters is not mediated by dopaminergic neurons, since the effect is also seen in retinas depleted of dopaminergic neurons. Phorbol esters also initiate the formation of spinules in synaptically isolated horizontal cells, demonstrating that they have a direct action on these cells. In addition, isolated horizontal cells have substrate proteins that are phosphorylated in a protein kinase C-dependent manner.

Adaptation, Physiological↗
PubMed1990

Endogenous dopamine and cyclic events in the fish retina, I: HPLC assay of total content, release, and metabolic turnover during different light/dark cycles.

In this study, we investigated the potency of dopamine for being an intrinsic signal for cyclic events in the fish retina. Dopaminergic activity was measured during different light/dark cycles, during continuous darkness, and during short-term light and dark adaptation within 1 h. During a 12-h light/12-h dark cycle, the total content of endogenous dopamine was high during the dark phase and low during the light phase. The potassium-induced release of endogenous dopamine followed a parallel time course. The concentration of the dopamine breakdown product 3,4-dihydroxyphenylacetic acid (DOPAC), which reflects the endogenous dopaminergic activity, was high during the light phase and low during the dark phase. Similar alterations occurred in accelerated 6-h light/6-h dark cycles, again indicating a strong coupling of dopaminergic activity with light. The cyclic alterations in the total endogenous dopamine content persisted during continuous darkness after an entrainment of the fish to a 12-h light/12-h dark cycle. Although the magnitude of the change was weaker, changes in dopamine content, potassium-induced dopamine release, and DOPAC were also measured during 1 h of light or dark adaptation. During a 1-h period of dark adaptation, the total content of dopamine and the potassium-induced release of endogenous dopamine increased, while DOPAC values decreased. These values changed in the opposite direction during 1 h of light adaptation. Our findings strongly suggest that dopamine is the intrinsic signal for light during both the light and dark phases and during short-term adaptation. Light seems to be the major trigger for dopaminergic activity within the fish retina.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Endogenous dopamine and cyclic events in the fish retina, II: Correlation of retinomotor movement, spinule formation, and connexon density of gap junctions with dopamine activity during light/dark cycles.

In the fish retina, retinomotor movement, spinule formation, and alteration of connexon density within gap junctions occur in response to changes in ambient light conditions. All of these morphological parameters can also be influenced by the application of dopamine. This study examines whether the morphological alterations of these structures are correlated with the activity of endogenous dopamine during an entrained 12-h light/12-h dark cycle and after 1-h sort-term adaptation periods. The two measured parameters of retinomotor movement, cone inner segment length and pigment dispersion, were well-correlated with endogenous cyclic dopamine activity. However, retinomotor movement was initiated already at the end of the entrained dark period, before the onset of light and before the onset of dopamine turnover. Furthermore, a 1-h dark-adaptation period in the middle of the light phase reduced dopamine activity but did not affect retinomotor movement. At the switch from light to dark and after a 1-h light period at midnight retinomotor movement correlated exactly with dopamine turnover and illumination conditions. The formation of spinules was correlated with dopaminergic activity during all phases of the light/dark cycle and during short-term adaptation periods. Spinules were expressed in the light when dopamine activity was high and they were retracted when dopamine activity was reduced during darkness. Connexon density of horizontal cell gap junctions showed a weaker correlation with the endogenous dopamine turnover. In this case, a high activity of endogenous dopamine was paralleled by a high density of connexons. Our results suggest that endogenous dopamine is involved in the cyclic regulation of the observed morphological alterations and that dopamine is part of the light signal for these mechanisms.

Animals↗
PubMed1989

Reduced light responsiveness of the cone pathway during prolonged darkness does not result from an increase of dopaminergic activity in the fish retina.

Dopaminergic activity in the fish retina during prolonged darkness was analyzed by monitoring total dopamine (DA) content, dihydroxyphenylacetic acid (DOPAC) and endogenous release of DA. Whereas DOPAC values drop to a third within the first 90 min of darkness, the releasable pool of DA increases by a third during this period. Endogenous release of DA drops to about 25% within the first 30 min and remains at this low level during continuous darkness. These data demonstrate that the electrophysiologically observed sensitivity reduction of horizontal cells during prolonged darkness is not due to an increase of dopaminergic activity during this period.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Glutamate and dopamine modulate synaptic plasticity in horizontal cell dendrites of fish retina.

Horizontal cell dendrites protruding into the cone pedicles in fish retina exhibit a light-dependent plasticity. In a light-adapted retina they form numerous spinules having membrane densities at their tips. These spinules disappear during dark adaptation. Experiments with light- or dark-adapted retinas which were incubated in glutamate or its agonists and antagonists, respectively, revealed that this putative cone transmitter is able to reduce the expression of spinules in a light-adapted retina. Dopamine, on the other hand, induces the formation of spinules in a dark-adapted retina and haloperidol reduces the expression in a light-adapted retina. These data suggest a control of spinules plasticity through two retinal neurotransmitter systems.

Animals↗