Biomedical subjects

J Kremers

Publications and source records attributed to J Kremers.

At least 19 recordsLinked to original sources

PubMed2002

M-cone opsin gene number does not correlate with variation in L/M-cone sensitivity.

Molecular genetic studies demonstrate that the human cone opsin gene array on the q-arm of the X-chromosome typically consists of one long-wave-sensitive (L) cone opsin gene and from one to several middle-wave-sensitive (M) cone opsin genes. Although the presence of the single L-cone opsin gene and at least one M-cone opsin gene is essential for normal red-green colour discrimination, the function of the additional M-cone opsin genes is still unclear. To investigate whether any variations in phenotype correlate with differences in the number of M-cone opsin genes, we selected 13 normal trichromat males, for whom four independent molecular techniques have exactly determined their number of M-cone opsin genes, ranging from one to four. Their phenotype was characterized by estimating their foveal L- to M-cone ratio from heterochromatic flicker photometric (HFP) thresholds, by measuring the wavelength corresponding to their 'unique yellow', and by determining their L- and M-cone modulation thresholds (CMTs). No correlation was found between these psychophysical measures and the number of M-cone opsin genes. Although, we found a reasonably good correlation between the L/M-cone ratios based on HFP and on CMT, we did not find any correlation between the estimated L/M-cone ratios and the settings of 'unique yellow'. Our results accord with previous molecular genetic studies that suggest that only the first two genes in the X-linked opsin gene array are expressed.

Color Perception↗

PubMed2001

Macular dystrophy with protan genotype and phenotype studied with cone type specific ERGs.

PURPOSE: To determine the L- and M-cone driven ERG responses in a male patient with macular dystrophy and a protan phenotype. METHODS: We measured large field ERG thresholds to stimuli which modulated exclusively the L- or the M-cones or the two in various combinations (both in-phase and in counterphase). In none of the stimuli, the S-cones were modulated. Additionally, standard and multifocal ERGs were measured. Analysis of the L- and M-cone pigment genes was performed by means of PCR, RFLP analysis and DNA sequencing techniques. RESULTS: Macular dystrophy was revealed by the markedly abnormal multifocal ERGs in presence of near normal standard ERGs. The large field ERG responses were exclusively driven by the M-cones with enlarged thresholds when compared with otherwise normal protanopes. In addition, the M-cone driven ERG response phases were abnormal. Pigment gene analysis confirmed a protan genotype with the presence of a single 5'red/3'green hybrid pigment gene. CONCLUSIONS: Our novel stimulus technique allows a reliable analysis of the separate cone pathways even in cases with macular dysfunction. The increased thresholds and the abnormal phase behavior of the M-cone driven ERGs reflect altered mechanisms of the retinal physiology in this patient. The data strongly suggest that the macular dystrophy and the protanopia have independent origins.

Adult↗

PubMed2001

Influence of contrast on the responses of marmoset lateral geniculate cells to drifting gratings.

The responses of lateral geniculate nucleus (LGN) cells in the common marmoset (Callithrix jacchus) to drifting luminance or cone isolating gratings of different spatial frequencies and contrasts were measured. The response noise, defined as the variability of the responses to single sweeps in the complex plane, was independent of stimulus contrast and spatial frequency but increased with increasing overall responsiveness of the cell. The signal-to-noise ratio of parvocellular (PC) cells was smaller than of magnocellular (MC) cells. At each contrast, the response amplitude as a function of spatial frequency could be described with a difference of Gaussians model. With this model, the sizes and the peak sensitivities of the receptive field centers and surrounds were estimated. It was found that receptive field center and surround sizes of LGN cells decrease slightly with increasing contrast. Further, the peak sensitivity decreases with increasing contrast. The two factors are involved in a decrease in responsivity (the response per unit contrast) with increasing contrast which is compatible to response saturation for low spatial frequency stimuli. PC cells did not saturate as much to luminance stimuli although some saturation was found with cone isolating gratings. We found that the response phase lag of both PC and MC cells decreased with increasing contrast, which cannot be explained on the basis of linear response behavior. Apparently the phase of LGN cell responses to drifting gratings is altered in comparison with the retinal inputs by additional nonlinearities.

Animals↗

PubMed2001

L- and M-cone-driven electroretinograms in Stargardt's macular dystrophy-fundus flavimaculatus.

PURPOSE: To study the dynamics of the long (L)- and middle (M)-wavelength-sensitive cone-driven pathways and their interactions in patients with Stargardt's macular dystrophy-fundus flavimaculatus (SMD-FF) and to correlate them with other clinical parameters and individual genotypes. METHODS: Forty-seven patients with SMD-FF participated in the study. In addition to standard 30-Hz flicker electroretinograms (30-Hz fERG), ERG responses were measured to stimuli that modulated exclusively the L or the M cones (L/M cones) or the two simultaneously. Blood samples were screened for mutations in the 50 exons of the ABCA4 gene. RESULTS: Patients with SMD-FF did not show a decrease in the mean L/M-cone-driven ERG sensitivity, but there was a significant increase in the interindividual variability. The mean L-/M-cone weighting ratio was normal. However, the L-cone-driven ERG was significantly phase delayed, whereas the M-cone-driven ERG was significantly phase advanced. These phase changes were significantly correlated with disease duration. The amplitude and implicit time of the standard 30-Hz fERG both correlated significantly with the L/M-cone-driven ERG sensitivity and with the phase difference between the L/M-cone-driven ERGs, indicating the complex origin of the standard 30-Hz fERG. Probable disease-associated mutations in the ABCA4 gene were found in 40 of 45 patients, suggesting that they form a genetically fairly uniform SMD-FF study group. There was no correlation between the genotype and the L/M-cone-driven ERGS: CONCLUSIONS: The changes in L/M-cone-driven ERG sensitivity and phase possibly represent two independent disease processes. The phase changes are similar to those found in patients with retinitis pigmentosa and possibly are a general feature of retinal dystrophies.

ATP-Binding Cassette Transporters↗

PubMed2000

Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

Animals↗

PubMed2000

L- and M-cone driven ERGs are differently altered in Best's macular dystrophy.

To study the L- and M-cone pathways and their interactions in patients with Best's macular dystrophy (BMD), ERG response thresholds were measured to stimuli which modulated exclusively the L- or the M-cones, or both in various combinations. The ERG threshold data could be described with a vector addition model. Compared with normals, BMD patients showed generally larger amplitudes of the L-cone driven ERGs. However, the M-cone driven ERGs were similar in amplitude but significantly phase advanced. The data confirm our previous observations that L- and M-cone pathways can be affected differently by retinal degeneration, despite their large physiological and biochemical similarities.

Adolescent↗

PubMed2000

L/M cone ratios in human trichromats assessed by psychophysics, electroretinography, and retinal densitometry.

Estimates of the relative numbers of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones vary considerably among normal trichromats and depend significantly on the nature of the experimental method employed. Here we estimate L/M cone ratios in a population of normal observers, using three psychophysical tasks-detection thresholds for cone-isolating stimuli at different temporal frequencies, heterochromatic flicker photometry, and cone contrast ratios at minimal flicker perception--as well as flicker electroretinography and retinal densitometry. The psychophysical tasks involving high temporal frequencies, specifically designed to tap into the luminance channel, provide average L/M cone ratios that significantly differ from unity with large interindividual variation. In contrast, the psychophysical tasks involving low temporal frequencies, chosen to tap into the red-green chromatic channel, provide L/M cone ratios that are always close to unity. L/M cone ratios determined from electroretinographic recordings or from retinal densitometry correlate with those determined from the high-temporal-frequency tasks. These findings suggest that the sensitivity of the luminance channel is directly related to the relative densities of the L and the M cones and that the red-green chromatic channel introduces a gain adjustment to compensate for differences in L and M cone signal strength.

Color Perception↗

PubMed2000

Large phase differences between L-cone- and M-cone-driven electroretinograms in retinitis pigmentosa.

PURPOSE: To study the dynamics and interactions of the signals originating in the long- (L-) and middle (M)-wavelength-sensitive cone pathways in patients with retinitis pigmentosa (RP). METHODS: Twenty-six patients with RP and 29 normal subjects participated in the study. Electroretinographic (ERG) responses were measured to stimuli that modulated exclusively the L- or the M-cones or the two simultaneously (both in-phase and in counter-phase) with varying ratios of L- to M-cone contrasts. S-cones were not modulated. RESULTS: The data of the normal subjects and of the patients can be described by a model in which the amplitudes and the phases of the signals originating in the L- and M-cones are vector summed. In the RP patients, there was a general reduction in ERG sensitivity. The L-cone-driven ERG response was significantly delayed, whereas the M-cone-driven ERG response was phase advanced. CONCLUSIONS: Large dynamic differences between L- and M-cone-driven ERGs can be detected in RP. As a result, the interaction between the L- and M-cone systems, when modulated simultaneously at 30 Hz, is subtractive in RP patients and additive in normal subjects. Our data show that the use of only a standard white flicker ERG might lead to a misinterpretation of the mechanisms involved in retinal disorders, because the phases of different cone-driven responses are not considered.

Adolescent↗

PubMed1999

Rod-cone-interactions in deuteranopic observers: models and dynamics.

We studied the interactions between rods and L-cones in deuteranopic human observers by stimulating the photoreceptors independently. Thresholds were determined using a PEST procedure for different ratios of rod to L-cone modulation without modulating the S-cones. Modulation frequency was either 2 or 10 Hz and the retinal illuminance ranged from 4.7 to 470 td (10.9-1090 scot td). We measured at 2, 7.5 and 20 degrees retinal eccentricity. The threshold data could be described by a model based on a vector addition of responses originating in the rods and the L-cones. The relative strength of rod signals relative to the L-cone signals increased with increasing retinal eccentricity and decreasing retinal illuminance. At 20 degrees eccentricity, rod and cone signals were of about equal magnitude at retinal illuminances as high as 470 td. Temporal frequency did not have a large effect on the ratio of rod to L-cone signal strength.

Adult↗

PubMed1999

Cone signal contributions to electroretinograms [correction of electrograms] in dichromats and trichromats.

PURPOSE: To find out how the different cone types contribute to the electroretinogram (ERG) by quantifying the contribution of the signal pathways originating in the long (L-) and the middle (M-) wavelength-sensitive cones to the total ERG response amplitude and phase. METHODS: ERG response amplitudes and phases were measured to cone-isolating stimuli and to different combinations of L- and M-cone modulation. Conditions were chosen to exclude any contribution of the short wavelength-sensitive (S-) cones. The sensitivity of the ERG to the L and the M cones was defined as the cone contrast gain. RESULTS: In the present paper, a model is provided that describes the ERG contrast gains and ERG thresholds in dichromats and color normal trichromats. For the X-chromosome-linked dichromats, the contrast gains of only one cone type (either the L or the M cones) sufficed to describe the ERG thresholds for all stimulus conditions. Data suggest that the M-cone contrast gains of protanopes are larger than the L-cone contrast gains of deuteranopes. The response thresholds of the trichromats are modeled by assuming a vector summation of signals originating in the L and the M cones. Their L- and M-cone contrast gains are close to a linear interpolation of the data obtained from the dichromats. Nearly all trichromats had larger L- than M-cone contrast gains. Data from a large population of trichromats were examined to study the individual variations in cone weightings and in the phases of the cone pathway responses. CONCLUSIONS: The data strongly suggest that the missing cone type in dichromats is replaced by the remaining cone type. The mean L-cone to M-cone weighting ratio in trichromats was found to be approximately 4:1. But there is a substantial interindividual variability between trichromats. The response phases of the L- and the M-cone pathways can be reliably quantified using the response phases to the cone-isolating stimuli or using a vector addition of L- and M-cone signals.

Adolescent↗

PubMed1998

Post-receptoral mechanisms of colour vision in New World primates.

Diurnal platyrrhines, both di- and trichromats, have magnocellular (M-) and parvocellular (P-) retinal ganglion cells which are morphologically very similar to those found in catarrhines. Catarrhine central P ganglion cells contact single midget bipolar cells, which contact single cones. Physiological recordings of retinal ganglion cells of dichromatic Cebus monkeys showed very similar cell properties to the catarrhine macaque, except that P ganglion cells lacked colour-opponency. We describe the presence of single-headed midget bipolar cells in the Cebus retina. These midget bipolar cells have axon terminal sizes in the same range as the dendritic tree sizes of P ganglion cells as far as 2 mm of retinal eccentricity. This result supports the view that, as in catarrhines, central P ganglion cells of platyrrhines receive input from single midget bipolar cells which in turn, receive input from single cones. This finding is consistent with the idea that a P pathway with one-to-one connectivity was present in the anthropoid ancestor before the divergence between catarrhines and platyrrhines.

Action Potentials↗

PubMed1998

Comparative retinal physiology in anthropoids.

During the last decade it has become clear that colour vision in platyrrhines (New World monkeys) differs from the uniform trichromatic pattern normally found in catarrhines (Old World monkeys, apes and human). Colour vision in most platyrrhine species is polymorphic, with many dichromatic individuals. The comparison of response properties in retinal ganglion cells and lateral geniculate cells between catarrhines and playrrhines elucidates how the evolution of trichromatic colour vision influenced the post-receptoral processing. We find that spatial and temporal processing is very similar in the platyrrhine and catarrhine retina, strongly suggesting that the retinal structure and function, found in living anthropoids, was already present in their common ancestor.

Action Potentials↗

PubMed1998

Flicker cone electroretinogram in dichromats and trichromats.

To measure cone signal strengths in the flicker electroretinogram (ERG) of dichromats and trichromats, we developed a set of flickering stimuli (30 Hz), which excite the middle-wavelength-sensitive (M-) and long-wavelength-sensitive (L-) cones independently. ERG responses to eight different ratios of L- to M-cone contrasts were recorded from each subject. The short-wavelength-sensitive (S-) cone contrast was 0% in all measurements. The recordings were Fourier analyzed to determine the amplitude of the fundamental component. ERG threshold values for each subject resulted in ellipses when plotted in an L-/M-cone contrast space. As expected, the orientations of the threshold ellipses of the protanopes (N = 2) were parallel to the L-cone axis, whereas those of the deuteranopes (N = 2) were parallel to the M-cone axis. For the trichromats (N = 5), there was considerable interindividual variation in ellipse orientation.

Adult↗

PubMed1998

Response phase of the flicker electroretinogram (ERG) is influenced by cone excitation strength.

We measured electroretinogram (ERG) response phases at different cone contrasts in trichromats and dichromats to investigate the dynamics of the long-wavelength-sensitive (L-) and middle-wavelength-sensitive (M-) cone pathways. ERG responses to stimuli, temporally modulated at 30 Hz, were recorded. The stimuli were generated on a computer controlled colour monitor. Thirty-two different combinations of L- and M-cone excitation strength, expressed as cone contrasts, were presented. The short-wavelength-sensitive (S-) cones were not stimulated (S-cone contrast = 0%). The response phase of the fundamental stimulus component was obtained from Fourier analysis. The ERG response phase lags decreased with increasing cone contrast. This was observed in all subjects with a normal appearing fundus. In dichromats and trichromats at low and intermediate contrasts, the phase lags to M-cone isolating conditions were smaller than those to L-cone isolating stimuli. In one dichromat with extreme myopia and cupping of the optic disc, the ERG phase lags increased with increasing cone contrast. The ERG response phase may be potentially useful for detecting retinal abnormalities.

Color Vision Defects↗

PubMed1997

Receptive field dimensions of lateral geniculate cells in the common marmoset (Callithrix jacchus).

We measured the spatial receptive field dimensions of cells in the lateral geniculate nucleus (LGN) of the common marmoset (Callithrix jacchus) using a bipartite field stimulus in which the two halves of the field were modulated identically but in counterphase. Horizontal and vertical edges between the two fields were positioned at different locations in the receptive field. By assuming that centers and surrounds have gaussian profiles, we were able to obtain a satisfactory mathematical description of the data. Receptive field centers were about a factor 1.6 larger than those of macaque LGN cells, in accordance with the smaller marmoset eye. There was a limited correspondence with dendritic tree dimensions of marmoset retinal ganglion cells. We further found that center and surround gaussians were not always concentric, and that the centers of some cells were elongated. This might allow some direction or orientation biases in LGN cells.

Algorithms↗

PubMed1997

Temporal properties of marmoset lateral geniculate cells.

We measured the temporal modulation transfer functions (TMTFs) of cells in the marmoset lateral geniculate nucleus (LGN) at three different luminance levels, and described the responses with a linear model. It was found that qualitatively there are many similarities with the temporal response properties of macaque and marmoset retinal ganglion cells. M-cells displayed stronger attenuation at lower temporal frequencies, and showed more nonlinearities (such as saturation and a contrast gain control) than P-cells. We therefore propose that the temporal properties of the visual system of New and Old World monkeys are similar at least up to the LGN. However, there are some quantitative differences, indicating that response alterations take place at the stage of synaptic transmission in the LGN. The most important are an attenuation of the responses to higher temporal frequencies and the smaller differences between parvo- and magnocellular cell responsivities. Cell responses to square-wave modulation were also measured and compared with predictions from a linear systems analysis. The linear systems analysis gave reasonable predicted responses to square-wave modulation, but these predictions were poor than those for retinal ganglion cells, indicating that additional nonlinearities are introduced at the synaptic transition in the LGN.

Animals↗

PubMed1997

Rod inputs to macaque ganglion cells.

The strength of rod inputs to ganglion cells was assessed in the macaque retina at retinal positions within 3-15 deg eccentricity. The experimental paradigm used temporally modulated heterochromatic lights whose relative phase was varied. This paradigm provided a sensitive test to detect rod input. In parvocellular (PC) pathway cells, the gain of the cone-driven signal decreased with decrease in luminance. At 2 td a weak rod response, of a few impulses per second for 100% rod modulation, was revealed in about 60% of cells. For blue-on cells, the cone-driven response also decreased with retinal illuminance, but no rod response could be found. In magnocellular (MC) pathway cells, rod input was much more apparent. Responses became rod dominated at and below 20 td; we cannot exclude rod intrusion at higher retinal illuminances. Responsivity was maintained even at low retinal illuminances. Temporal-frequency dependent rod-cone interactions were observed in MC-pathway cells. Rod responses were of longer latency than cone responses, but there was no evidence of any difference in rod latency between parvocellular and magnocellular pathways.

Animals↗

PubMed1996

The time course of adaptation in macaque retinal ganglion cells.

The time course of adaptation of cells of the parvocellular (PC) and magnocellular (MC) pathways has been characterized following changes in retinal illuminance or chromaticity. Adaptation state was cycled between high and low luminance levels or between backgrounds with wavelengths metameric to 630 and 570 nm. Cell responsivity was probed with brief bursts of luminance or chromatic modulation. After a change in luminance, adaptation of both MC-cells (tested with a luminance probe) and red-green PC-cells (tested with a chromatic probe) was relatively rapid and largely complete within 100 msec or less. After a change in chromaticity, recovery of responsivity in red-green PC-cells was dependent on cell type. Recovery of responsivity with backgrounds elevating maintained firing was complete within a few seconds, but with backgrounds suppressing cell firing, recovery took many tens of seconds. This very slow time course may be due to a threshold effect. In experiments with backgrounds which selectively adapted one cone type, use of cone-isolating probes indicated that the time course of PC-cell chromatic adaptation may be determined at a site after the subtraction of cone signals. Recovery of responsivity of MC-cells was also prolonged over several seconds following a chromatic change. Our data suggest that adaptation in macaque ganglion cells depends on mechanisms both before and after the site of cone interaction, and that these mechanisms may differ in time course between MC- and PC-cells. The results indicate that it may be important in psychophysical adaptation experiments to consider the presence of multiple postreceptoral mechanisms with different adaptation characteristics.

Adaptation, Ocular↗