The value of electrophysiological testing in glaucomatous diseases.
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Animals↗
Biomedical subjects
M Korth
Publications and source records attributed to M Korth.
Protein phosphatase 2A is essential for the activation of Ca2+-activated K+ currents by cGMP-dependent protein kinase in tracheal smooth muscle and Chinese hamster ovary cells.
The regulation of Ca2+-activated K+ channels (KCa channels) by cGMP-dependent protein kinase (cGMP kinase) and its molecular mechanism were investigated in Chinese hamster ovary (CHO) and tracheal smooth muscle cells. In CHO wild-type cells (CHO-WT cells) and in CHO cells stably transfected with cGMP kinase Ialpha (CHO-cGK cells), KCa channels with intermediate conductance (approximately 50 picosiemens) were identified. Due to the basal activity of cGMP kinase, Ca2+-activated K+ currents had a higher sensitivity toward the cytosolic Ca2+ concentration in CHO-cGK cells than in CHO-WT cells. Dialysis of the active fragment of cGMP kinase (300 n) into CHO-WT cells or of cGMP into CHO-cGK cells increased the Ca2+-activated K+ current, while the catalytic subunit of cAMP-dependent protein kinase (cAMP kinase) was without effect. In cell-attached patches obtained from freshly isolated bovine tracheal smooth muscle cells, the open state probability (NPo) of maxi-KCa channels (conductance of approximately 260 picosiemens) was enhanced by 300 microM 8-(4-chlorophenylthio)-cGMP, a specific and potent activator of cGMP kinase. In contrast, 1 microM isoprenaline, 20 microM forskolin, and 3 mM 8-bromo-cAMP failed to enhance KCa channel activity. In excised inside-out patches, only the active fragment of cGMP kinase (but not that of cAMP kinase) increased NPo when applied to the cytosolic side of the patch. The enhancement of NPo by cGMP kinase was inhibited in CHO cells as well as in tracheal smooth muscle cells by the cGMP kinase inhibitor KT 5823 (1 microM) and the protein phosphatase (PP) inhibitors microcystin (5 microM) and okadaic acid (10 nM). The catalytic subunit of PP2A (but not that of PP1) mimicked the effect of cGMP kinase on NPo in excised inside-out patches. The results show that cGMP kinase regulates two different KCa channels in two unrelated cell types by the same indirect mechanism, which requires the activity of PP2A. The regulation of the KCa channel is specific for cGMP kinase and is not mimicked by cAMP kinase.
Animals↗
Quadrant pattern ERG with SLO stimulation in normals and glaucoma patients.
BACKGROUND: The pattern ERG (PERG) is one of the promising methods for investigation of glaucoma and may detect it at an early stage. The purpose of this study was to test the usefulness of the scanning laser ophthalmoscope (SLO) as a stimulator for evoking quadrant PERGs under visual control in normal and glaucoma eyes. METHODS: The helium-neon laser of a Rodenstock SLO was used for quadrant stimulation (18 degrees x 29 degrees pattern size), while an infrared laser visualized the eye's fundus. Steady-state pattern-reversal ERGs were recorded in response to stripe patterns (8.33 Hz, 0.5 cycles/deg) in four retinal quadrants. Corresponding visual field defects were determined with the Octopus perimeter (G1, peridata). The subjects were 28 controls and 34 glaucoma patients with visual field losses and papillometric defects. RESULTS: Amplitudes of nasal retinal areas (which include the blind spot) are smaller than those of temporal ones, and temporal lower responses are the largest. PERG amplitudes of all quadrants are significantly reduced in glaucoma (sensitivity 82%, specificity 80%). The differences between upper and lower quadrant PERGs are correlated with the differences between localized visual field defects of the same areas, (r = 0.46, P = 0.02). CONCLUSIONS: The study demonstrates the feasibility of the SLO system for evoking localized PERG in normals and patients and shows the reduction of quadrant ERG amplitudes in glaucoma using the laser system.
Adult↗
Color axis evaluation of the Farnsworth Munsell 100-hue test in primary open-angle glaucoma and normal-pressure glaucoma.
BACKGROUND: It was the aim of the present study to analyze a separate color-axis evaluation of the Farnsworth Munsell 100-hue test (FM 100) in primary open-angle glaucoma (POAG) and normal pressure glaucoma (NPG). PATIENTS AND METHODS: One eye of each of 112 individuals (age 35-65 years, visual acuity > 20/28, myopia < -7.5 D) was included. The groups consisted of 62 normal subjects and 50 glaucoma patients (33 POAG and 17 NPG). We evaluated the FM 100 overall error score and the error scores of the protan, deutan and tritan axes. The results were compared with perimetric (Octopus G1 mean defect) and morphometric data of the optic disc. RESULTS: All error scores were significantly higher in the glaucoma group than in the normal group. In an age-related evaluation, differences were significant in age groups above 45 years. No significant differences were found between the POAG and NPG groups. The sensitivity of the overall score to identify glaucoma was 62% (specificity 80%). In the glaucoma group the overall score and the protan score increased significantly with the mean defect (r > 0.3, P < 0.01). Several scores increased slightly with decreasing neuroretinal rim area, but not on a significant level. Separate color-axis evaluations did not show any stronger correlations and did not reveal any differences between POAG eyes and NPG eyes. This was true even for the tritan axis error. CONCLUSIONS: Although FM 100 error scores are higher in glaucoma eyes and increase with glaucomatous damage, they do not separate well. In the sample of this study, separate color-axis evaluation did not improve the diagnostic value. With the FM100 a different pattern of color vision defects in POAG and NPG eyes could not be detected.
Adult↗
[Sensory physiology and biomorphology of the optic papilla: analysis of correlation in normal persons].
BACKGROUND: The aim of the present study was to investigate whether the morphological variability of the optic disc has an influence on sensory test procedures. PATIENTS AND METHODS: In 52 eyes of 52 normal persons psychophysical (perimetry, color vision, contrast sensitivity) and electrophysiological (pattern-ERG and pattern-VEP) tests and planimetric papillometry were performed. A correlation analysis was made between sensory tests and area of optic disc (1.79 to 5.2 mm2) and neuroretinal rim. RESULTS: There was no significant correlation between perimetry, color vision, pattern-ERG, pattern-VEP, spatio-temporal and temporal contrast sensitivity on the one hand and optic disc area or neuroretinal rim area on the other. CONCLUSION: Results of psychophysical and electrophysiological tests do not have to be corrected with respect to the neuroretinal rim area.
Adult↗
Differential class III antiarrhythmic effects of ambasilide and dofetilide at different extracellular potassium and pacing frequencies.
We studied the effect of two new class II antiarrhythmics, ambasilide and dofetilide, on the action potential duration (APD) of guinea pig right ventricular papillary muscle at different extracellular potassium concentrations ([K+e]) and pacing frequencies. Under normal [K+e], both drugs significantly prolonged APD90 (APD at 90% repolarization) at 0.5 Hz. The effect of ambasilide was well preserved at rapid pacing rates, independent of [K+e]. The effect of dofetilide was markedly reduced with increasing pacing rate, especially in high [K+e]. Therefore, ambasilide may be useful in treating tachyarrhythmias in normal, as well as in altered [K+e] conditions.
Action Potentials↗
Contrast-sensitivity testing with scanning-laser ophthalmoscope stimulation in normal, ocular hypertensive, and glaucomatous patients.
The purpose of this study was to test the usefulness of the scanning laser ophthalmoscope (SLO) as a stimulator for localized contrast-sensitivity (CS) measurements under visual control in normals and glaucomatous patients. The helium-neon laser (630 nm) of a Rodenstock SLO was used to generate a localized square-wave stripe pattern and a fixation mark while an infrared laser (780 nm) visualized the eye's fundus. Thus, measurements with unstable fixation could be discarded. The spatio-temporal CS was determined with a localized alternating pattern as follows: 5 Hz, 2.88 cycles/degree; stimulus diameter 2 degrees; test location central, temporal upper, and temporal lower retinal area. The subjects included 47 controls, 23 ocular hypertensive patients (intraocular pressure > 21 mmHg, normal optic disc, no visual field defect), 27 "preperimetric" glaucoma patients (intraocular pressure > 21 mmHg, early glaucomatous optic disc damage, no visual field defect), and 41 "perimetric" glaucoma patients with glaucomatous defects of the optic disc and perimetric losses. Nonparametric tests (Wilcoxon, Spearman) were used for statistical analyses. Among the three locations tested, CS values recorded for the temporal lower retinal areas showed the strongest reduction in glaucomas ("preperimetric" P = 0.002, "perimetric" P < 0.0001) and a significant correlation with the perimetric mean defect of the stimulated area (r = 0.65, P < 0.001). In all, 95% of glaucomatous eyes with extensive visual field losses were recognized as pathologic at a specificity of 80%. Spatiotemporal CS of temporal retinal areas is sensitive to glaucoma. The present study confirms the feasibility of using the SLO system for localized CS measurements, in normals and patients.
Adult↗
Effects of doxorubicin on excitation-contraction coupling in guinea pig ventricular myocardium.
Doxorubicin, an anticancer drug, was recently shown to release Ca2+ from cardiac sarcoplasmic reticulum (SR) by increasing the open probability of Ca2+ release channels. In the present study, we investigated the effects of doxorubicin on excitation-contraction coupling of guinea pig heart preparations. In papillary muscles contracting at 0.5 Hz, 100 mumol/L doxorubicin produced within 3 hours the following effects: it increased the force of contraction by 269.3 +/- 19.8% (n = 6) and prolonged the time to peak force by 75.1 +/- 8.7% (n = 6), relaxation time by 54.7 +/- 8.7% (n = 6), and action potential duration (APD) at 90% repolarization (APD90) by 38.6 +/- 2.9% (n = 3). Despite its positive inotropic effect, doxorubicin depressed the early contraction component by increasing the latency between stimulus and the onset of force development. In single myocytes, 100 mumol/L doxorubicin prolonged APD90 by 62.1% (n = 18) and blocked time-dependent delayed rectifier K+ current (IK) by 44% (n = 9). Ca2+ inward current and inward rectifier K+ current were not affected by doxorubicin. Ca2+ transients elicited in myocytes loaded with the fluorescent Ca2+ indicator fura 2 were strongly suppressed by doxorubicin in their initial rising phase. There-after, doxorubicin produced a delayed rise in intracellular Ca2+, which reached a late peak exceeding that of the control peak by 52 +/- 8% (n = 5). The results suggest that doxorubicin decreases Ca(2+)-induced Ca2+ release from cardiac SR, probably by increasing the SR Ca2+ leak. On the other hand, prolongation of APD due to inhibition of IK allows more Ca2+ to enter the cell. After being only temporarily buffered by the SR, Ca2+ may accumulate in the cytosol as long as depolarization is maintained and lead to a more complete activation of contractile proteins.
Action Potentials↗
Comparison of temporal and spatiotemporal contrast-sensitivity tests in normal subjects and glaucoma patients.
Contrast sensitivity (CS) is reduced in glaucoma diseases. This study compares the value of different CS measurements in glaucoma diagnosis. The study population consisted of age-matched groups of 31 normal subjects (age, 36-59 years; median, 47 years; mean +/- SD, 47.4 +/- 7 years) and 59 glaucoma patients with optic disk damage and visual field defects (age, 36-63 years; median, 53 years; mean +/- SD, 52.3 +/- 7 years). Three types of CS determination were carried out in all subjects: (1) temporal CS of a sinusoidally flickering light (37 Hz) in a ganzfeld bowl, (2) spatiotemporal CS (alternating pattern: 2.5 Hz, 1 cycle/degree; screen size, 5.3 degrees x 4.3 degrees) in a temporal upper retinal area (13.8 degrees horizontal, 4.2 degrees vertical), and (3) spatial CS of a static pattern (three spatial frequencies: 0.6, 3.0, and 12 cycles/degree; screen size, 5.3 degrees x 4.3 degrees) with central fixation. In glaucoma patients the results of CS tests with flickering stimuli were highly significantly correlated with the perimetric mean sensitivity (MS; Octopus G1 program: temporal CS, r = 0.67, P < 0.001; spatiotemporal CS, r = 0.8, P < 0.001). For spatial CS the frequency of 3.0 cycles/degree showed the strongest correlation with MS (r = 0.64, P < 0.001). Only the peripherally localized, spatiotemporal CS showed a strong correlation with optic disk damage (r = 0.59, P < 0.001). On the other hand, the full-field flicker test achieved the best separation between normal subjects and glaucoma patients (specificity, 90%; sensitivity, 71%). These results indicate that tests for temporal resolution are more sensitive to glaucoma defects than are tests for spatial resolution.
Adult↗
Differences between pattern-evoked electroretinograms obtained by a scanning laser ophthalmoscope and by a mechanical mirror system.
Pattern electroretinograms were studied in response to stripe patterns of different spatial frequencies and intensities in the pattern-onset and reversal mode by means of a scanning laser ophthalmoscope and a mechanical mirror system (maxwellian view). The stimulus conditions in both procedures were as close as possible: 31 degrees square field, 633-nm wavelength and the same equipment for recording. The remaining differences between the two methods were the line and pixel structure in the scanning laser ophthalmoscope and the buildup speed (40 ms in the scanning laser ophthalmoscope and less than 1 ms in the mirror system). This difference was reflected in the response peak times of the pattern electroretinogram, which were up to 10 ms in the scanning laser ophthalmoscope measurement. The pattern-related onset response was smaller with the scanning laser ophthalmoscope, indicating a strong sensitivity to the slow build-up speed, while the offset and reversal responses showed no differences in amplitudes. All differences were found only with the use of high luminances. The results suggest that responses evoked with patterns displayed on a television screen could be faster and larger if stimulators faster than the conventional television standard were used. Because of the smallness of onset amplitudes, the pattern-reversal mode might be better for stimulation in a clinical study when the scanning laser ophthalmoscope is used.
Adult↗
[Use of a new anomaloscope test in diagnosis of glaucoma].
BACKGROUND: The Color Vision Meter 712 (CVM) is a new automatic computerized anomaloscope relying on both the Rayleigh and the Moreland equation. In the present study the diagnostic value of Color Vision Meter was examined in glaucoma for the first time and was compared with the Farnsworth 100 hue test. PATIENTS AND METHODS: 33 normals, 15 patients with ocular hypertension (OHT) and a heterogenic group of 31 glaucoma patients were tested with the Nagel anomaloscope, the Color Vision Meter 712 and the Farnsworth 100 hue test. The following determinations were made in all subjects: 1. Anomalous quotient of the Rayleigh equation of the Nagel anomaloscope and of the Color Vision Meter, 2. Mean tritan score of 100 hue test, 3. The matching range, mid matching point, and anomalous quotient of the Moreland equation with the Color Vision Meter. RESULTS: While in the OHT group only the matching range of the Moreland equation was enlarged, all three variables (matching range, mid matching point and anomalous quotient) of the Moreland equation were significantly changed in the glaucoma group. The mean tritan score of the 100 hue test showed in the OHT group only a slight difference compared to normals, and in the glaucoma group a low significance and a low sensitivity. The matching range of the Moreland equation seems to be most useful with a sensitivity of 87.1% and a specificity of 93.6%. CONCLUSION: Our results show that the new anomaloscope Color Vision Meter 712 should be considered as a quick screening test for the examination of blue-color vision disturbances in glaucoma because of its higher sensitivity, its easier use for examiner and patients, and its shortened examination time (5 min per equation).
Adult↗
Scotopic threshold response and scotopic PII in glaucoma.
PURPOSE: The value of the ERG scotopic threshold response (STR), which is known to originate in the proximal retina and of the near-threshold scotopic PII(B-wave), was studied in glaucoma. METHODS: Full-field single flashes were presented under scotopic conditions in two subject groups, a glaucoma group (n = 30) and a normal control group (n = 35). The intensity level for evoking STR was where the maximum response occurs, whereas the intensity level for evoking scotopic PII was where the response begins to appear. RESULTS: The STR is only slightly reduced in glaucoma (P = 0.046), but scotopic PII is significantly diminished (P < 0.0001). CONCLUSIONS: The relatively intact STR in glaucoma suggests that structures responsible for its generation are less damaged in glaucoma than those responsible for scotopic PII.
Dark Adaptation↗
VEP test of the blue-sensitive pathway in glaucoma.
PURPOSE: The blue-sensitive pathway in normal subjects and in patients with primary open-angle glaucoma (POAG) was tested with the pattern visual evoked potential (VEP) method under selective adaptation. METHODS: Recording of pattern-onset VEP in response to blue (460-nm) stripes (0.88 c/deg) presented either without or with a bright yellow (570-nm) adaptation light (Maxwellian view, 33 degree diameter). Amplitude and peak times were evaluated, and the mean tritan score of the Farnsworth 100-hue test was determined. Age-matched normal subjects (n = 34) and (n = 32) patients with POAG were examined. RESULTS: The amplitude and peak time of the VEP without selective adaptation did not discriminate normal subjects from the POAG group. With selective adaptation, the amplitude was reduced (P = 0.002) and its peak time delayed (P < 0.0001) in POAG, yielding a sensitivity of 75% and a specificity of 94%. The VEP measures only under selective adaptation correlated significantly in patients with POAG with the mean perimetric defect, with the optic disc damage, and with the 100-hue test. CONCLUSIONS: Recording the blue-on-yellow VEP is a useful test in glaucoma research.
Adult↗
Transfected cGMP-dependent protein kinase suppresses calcium transients by inhibition of inositol 1,4,5-trisphosphate production.
cGMP is a key regulatory molecule in visual transduction, integration of neuronal response to excitatory neurotransmitters, relaxation of smooth muscle, intestinal secretion of water and salt, and reabsorption of sodium and water in the distal tubules of the nephron. Some of these cellular functions are associated with the activation of cGMP kinase and a decrease in cytosolic calcium levels ([Ca2+]i). The mechanism by which cGMP kinase lowers [Ca2+]i is controversial. We have used CHO cells stably transfected with cGMP kinase to test several of the proposed [Ca2+]i-lowering mechanisms. Thrombin induces a calcium transient in wild-type and cGMP kinase-expressing CHO cells by releasing calcium from intracellular stores. Preincubation of wild-type cells with 8-bromo-cGMP had no effect on the calcium transient, whereas 8-bromo-cGMP prevented the thrombin-stimulated calcium transient in cGMP kinase-expressing CHO cells. In both cell types 8-bromo-cGMP had no effect on [Ca2+]i transients induced by replacing extracellular sodium by tetramethylammonium, ruling out an effect of cGMP kinase on Ca(2+)-ATPases. However, cGMP kinase activation effectively suppressed thrombin-induced stimulation of inositol 1,4,5-trisphosphate production. These results show that cGMP kinase lowers [Ca2+]i by interfering with the inositol 1,4,5-trisphosphate synthesis.
Animals↗
Utility of the color pattern-electroretinogram (PERG) in glaucoma.
Pattern-onset electroretinograms (PERGs) with red-green color contrast (CC) and green-"black" luminance contrast (LC) stripe patterns (0.3 c/deg) were recorded in a group of 80 control subjects and in a group of 42 patients having glaucomas of varying etiology and severity. The PERG data were correlated with the results of static perimetry and optic disc morphometry. In the glaucoma group the PERG was reduced significantly and by relatively similar amounts with both CC and LC stimuli. A significant correlation of the PERG reduction with visual field loss was found only with the CC, not with the LC PERG. Correlations between PERG amplitudes and neuroretinal rim areas of the optic disk were similar for the LC and for the CC stimulus. The rather poor percentage of correct classification of controls and patients based on the PERG or the optic disc morphometry alone can be improved by two-dimensional discriminant analysis using both CC PERG and papillometry data.
Color Perception↗
Spatial and chromatic interactions in the human pattern electroretinogram.
The spectral sensitivity and the spatial selectivity was studied both psychophysically and electroretinographically using the pattern onset-offset paradigm. All measurements were made under intensive yellow adaptation. The spectral sensitivity functions of both measures were in close agreement. They showed a peak at 460 nm (blue-sensitive mechanism) and a shoulder around 550 nm (red-green-sensitive mechanism). The luminance curves of the pattern onset ERG obtained with long wavelengths had a steeper slope and reached larger amplitudes than those obtained with short wavelengths. In addition the response-peak times were longer with short wavelengths. When the spatial frequency of the pattern was varied the 460 nm-onset responses showed very little or no spatial tuning and long peak times (around 60 msec). This was ascribed to the contribution from only one type of ganglion cell, namely the blue-yellow opponent receptive fields lacking a center-surround organization. The 550 nm-onset responses showed a clear spatial tuning (4 c/deg) and an increase in peak time (40-50 msec) with increasing spatial frequency (0.26-9.2 c/deg). This was ascribed to different types of receptive fields having a center-surround structure.
Adaptation, Ocular↗
Interactions of spectral, spatial, and temporal mechanisms in the human pattern visual evoked potential.
The human pattern onset-offset visual evoked potential (VEP) was studied with different colours and spatial frequencies presented on a steady homogeneous intensive yellow background. Under this condition a broad, late negative wave (N2) dominated by the blue-sensitive mechanism and a sharper earlier positive wave (P1) dominated by the red-green-sensitive mechanism can be observed. With a 460 nm pattern N2 shows a strong amplitude tuning at low-medium spatial frequencies. With 550 nm an early negative component (N1) is added showing an amplitude tuning at high spatial frequencies. Different spatial resolutions of the two colour mechanisms are thus indicated. With pattern-reversal stimuli the 550 nm stimulus shows a higher temporal resolution than the 460 nm stimulus.
Color Perception↗
[Simple rapid contrast sensitivity test in diagnosis of glaucoma].
BACKGROUND: Psychophysical tests employing high-frequency stimuli are becoming of increasing value in glaucoma diagnosis. In the present study a simple, quick, and sensitive flicker test is described which can be used as an screening examination for glaucoma. METHOD: A flicker test is described which uses a white sinusoidally flickering light presented at 37.1 Hz in a ganzfeld bowl under photopic conditions (ca 10 cd/m2. Fication is not necessary. The modulation (temporal contrast) of the flicker light is varied in small steps until flicker threshold is reached. The reciprocal of the threshold value represents the temporal contrast sensitivity. The test takes only about 5 min per eye. RESULTS: 69 eyes of 69 normals, 60 eyes of 60 ocular hypertensive (OHT), and 50 eyes of 50 patients with primary open angle glaucoma were statistically evaluated. The validation of the sensitivity in both eyes was 75.6% and the specificity was 85.9%. 41.7% of the OHT patients were classified as pathologic. CONCLUSIONS: Thus, the ganzfeld flicker test is a simple and quick (5 min) additional screening test in glaucoma.
Adult↗