Biomedical subjects

Claire S Barnes

Publications and source records attributed to Claire S Barnes.

6 recordsLinked to original sources

PubMed2003

Deficits in temporal integration for contrast processing in retinitis pigmentosa.

PURPOSE: The purpose of this study was to evaluate the properties of foveal temporal integration in patients with retinitis pigmentosa (RP) within the framework of contrast processing by the magnocellular (MC) and parvocellular (PC) pathways. METHODS: Temporal integration functions were measured in eight patients with RP whose visual acuities ranged from 20/25 to 20/63. Contrast thresholds were obtained at durations ranging from 15 to 480 ms, using steady-pedestal and pulsed-pedestal paradigms to bias performance toward the MC and PC pathways, respectively. The patients' results were compared with those of 10 age-similar control observers with normal vision. For both paradigms, contrast thresholds as a function of duration were fit with a two-limbed function to derive the critical duration for temporal integration (t(c)) and the asymptotic threshold at long durations (Delta L(infinity)). RESULTS: The log t(c)s of the patients with RP were significantly longer than those of the control subjects for the steady-pedestal paradigm (presumed MC-pathway mediation; t = 3.67, P < 0.001), but not for the pulsed-pedestal paradigm (presumed PC-pathway mediation; t = 0.76, P = 0.45). Further, the patients with RP showed a significant correlation between log t(c) and log Delta L(infinity) for the steady-pedestal paradigm (r = 0.72, P < 0.05) but not for the pulsed-pedestal paradigm (r = -0.37, P = 0.36). CONCLUSIONS: The patients with RP in this study showed greater deficits in contrast sensitivity and a more prolonged critical duration under test conditions that favor the MC rather than the PC pathway. A likely explanation is a high-frequency response attenuation at the level of the cone photoreceptors that has a differential effect on contrast-processing tasks that emphasize different postreceptoral mechanisms.

Adult↗

PubMed2003

ON-pathway dysfunction and timing properties of the flicker ERG in carriers of X-linked retinitis pigmentosa.

PURPOSE: Carriers of X-linked retinitis pigmentosa (XLRP) frequently show prolonged implicit times of the flicker electroretinogram (ERG). This study tested the hypothesis that a preferential response attenuation within the cone depolarizing (ON) bipolar cell (DBC) pathway is a major contributing factor. METHODS: Light-adapted, full-field ERGs were recorded from 10 XLRP carriers and 12 visually normal control subjects. Fundamental amplitudes and phases of ERG responses to sinusoidally flickering stimuli at temporal frequencies ranging from 8 to 96 Hz were analyzed within the framework of a recent vector summation model of the cone system ERG to test for evidence of a response attenuation within the DBC pathway. In addition, ERG responses to sawtooth flicker were examined for a reduced b- to d-wave amplitude ratio, indicative of ON pathway dysfunction. RESULTS: The carriers' fundamental response phases at 32 Hz correlated significantly with their log ratios of response amplitudes at 32 versus 12 Hz (r = 0.89, P < 0.001) and with their log b- to d-wave amplitude ratios (r = 0.71, P < 0.05), both of which were used as indices of response attenuation within the DBC pathway. A control experiment demonstrated that a reduced sensitivity of cone phototransduction made at most only a minimal contribution to the timing changes in the carriers' flicker ERG responses. CONCLUSIONS: The overall pattern of results indicates that a preferential response attenuation within the DBC pathway is the primary source of timing changes in the flicker ERGs of these carriers of XLRP. These findings illustrate the value of analyzing ERG responses to flickering stimuli at multiple temporal frequencies to evaluate mechanisms of disease action in photoreceptor degenerations.

Adolescent↗

PubMed2002

Simultaneous S-cone contrast.

Chromatic induction is the change in appearance of one light caused by a second, nearby light. We measured chromatic induction in a central test viewed within an inducing field that was varied in only short-wavelength-sensitive (S) cone stimulation. The observer matched the appearance of the central test by adjusting the chromaticity of a haploscopically presented comparison field, seen by the other eye on a dark background. When the central test weakly stimulated S cones, the S-cone level in the surround caused little change in the color appearance of the test. When the central test substantially stimulated S cones, on the other hand, the appearance of the center showed S-cone contrast: raising the level of S in the surround reduced the level of S set to match the central test. Further, a surround that weakly stimulated S cones raised the matching S-cone level above that required without a surround (dark-adapted condition). These results cannot be explained by S-cone sensitivity loss or by a two-process model of adaptation. A cortical mechanism is proposed to mediate S-cone antagonism.

Color Perception↗

PubMed2002

A distinctive form of congenital stationary night blindness with cone ON-pathway dysfunction.

PURPOSE: To characterize a distinctive form of congenital stationary night blindness (CSNB). DESIGN: Observational case report. PARTICIPANTS: A 30-year-old male with a history of night blindness, several members of his family, a patient with "complete" congenital stationary night blindness (CSNB1), and groups of age-similar control subjects. METHODS: Rod-system function was evaluated by measuring psychophysical dark-adapted thresholds, by recording dark-adapted electroretinograms (ERGs), and by fundus reflectometry. Cone-system function was evaluated by recording light-adapted ERGs, including those to sawtooth flicker, and by recording light-adapted visually evoked potentials (VEPs) to luminance increments and decrements. MAIN OUTCOME MEASURES: Dark-adapted thresholds, ERGs, rhodopsin double densities, Goldmann visual fields, and VEPs. RESULTS: The patient's visual acuity, visual fields, and color vision were normal. His peripheral dark-adapted thresholds were rod-mediated but elevated by approximately 3 log units above normal. Rhodopsin double density and bleaching recovery were normal. His dark-adapted maximal-flash ERG showed a "negative" waveform, in which the b-wave was more reduced in amplitude than the a-wave, although the a-wave amplitude was also reduced. The rod photoreceptors contributed to the patient's dark-adapted ERGs, as illustrated by the unequal responses to cone-matched stimuli. The patient's cone-mediated thresholds for long-wavelength stimuli were within the normal range. However, his light-adapted brief-flash b-wave was abnormal in amplitude and implicit time. Selective abnormalities of the ON responses of the cone system were apparent in the patient's reduced b-wave amplitude to rapid-on flicker with a normal response to rapid-off flicker, and his prolonged VEP latencies to increments but not to decrements. CONCLUSIONS: The overall pattern of findings distinguishes this patient from previously described forms of CSNB. The results suggest that two factors likely contribute to the patient's night blindness: (1) a rod phototransduction defect and (2) a postreceptoral defect. The results also indicate dysfunction within the cone ON pathway.

Adult↗

PubMed2002

Nature of the cone ON-pathway dysfunction in melanoma-associated retinopathy.

PURPOSE: To establish the basis for an ON-pathway abnormality of the cone system in melanoma-associated retinopathy (MAR) through analysis of the electroretinogram (ERG) and visual evoked potential (VEP). METHODS: Two patients with MAR syndrome whose sera produced immunolabeling of retinal bipolar cells participated in the study. Full-field ERGs were recorded in response to brief flashes, to rapid-on and rapid-off sawtooth stimuli at a temporal frequency of 8 Hz, and to sine-wave stimuli at temporal frequencies ranging from 8 to 96 Hz. Fundamental responses to the sine-wave stimuli were evaluated within the context of a vector-summation model of the depolarizing bipolar cell (DBC) and hyperpolarizing bipolar cell (HBC) contributions to the response fundamental. VEPs were recorded to the onset of luminance increments and decrements that had contrasts of 10%, 20%, and 50%. The patients' results were compared with those of age-similar control subjects. RESULTS: The patients with MAR showed abnormal ERG responses to luminance increments, consisting of a marked attenuation of the initial portion of the b-wave, but their ERG responses to luminance decrements were normal in amplitude and timing. The ERG temporal response functions of the patients with MAR had normal amplitudes at frequencies of 32 Hz and higher, with a constant phase lag across these frequencies, but larger-than-normal amplitudes at frequencies below 32 Hz, and a phase lead at 8 Hz. Their VEP responses showed a marked delay to increments but only a minimal delay to decrements. CONCLUSIONS: Within the context of the vector-summation model, the ERG findings in the patients with MAR are more consistent with an attenuation of the DBC contribution to the ERG response than with a DBC response delay. The delayed VEP responses of the patients with MAR to luminance increments may represent a late response of the OFF system to increment onset.

Adolescent↗

PubMed2002

Mutated alleles of the rod and cone Na-Ca+K-exchanger genes in patients with retinal diseases.

PURPOSE: To study the possible involvement of the rod (SLC24A1) and cone (SLC24A2) Na-Ca+K exchanger (NCKX) genes in retinal diseases. METHODS: DNA was collected from unrelated patients with retinal disease, mainly from North America. A human genomic library was screened with the cone NCKX cDNA, and hybridizing clones were sequenced to determine the genomic organization of the SLC24A2 gene. The single-strand conformation polymorphism (SSCP) technique and direct sequencing were used to screen the patients' DNA for mutations in SLC24A1 and SLC24A2. The effect of selected missense changes on protein function was tested by measuring potassium-dependent Na-Ca exchange of the mutant proteins expressed in insect cells. RESULTS: Twenty-seven novel sequence changes were found in the rod NCKX gene, 21 of which are unlikely to be pathogenic, because they did not cosegregate with the disease or did not affect conserved regions of the protein. Of the remaining six, two were frameshift mutations found in one patient each. If translated, these alleles would encode nonfunctional proteins. Three of the six possibly pathogenic mutations were missense changes located in conserved regions, and their protein functions were assayed. Only one (Ile992Thr) had a significantly low level of exchanger function, but it was found in two unrelated patients who were heterozygotes with different retinal diseases, and this mutation could not be unequivocally associated with either disease. The last of the six changes is likely to create a new splice acceptor site. The genomic organization of the cone NCKX gene was determined, and it contained 11 exons with a few splice variants. Fifteen novel sequence changes were identified in the cone exchanger gene in patients with a cone dysfunction or degeneration. Only three of these sequence changes, all missense changes found in heterozygous patients, were considered possibly pathogenic. Functional analysis showed only a slight reduction in the activity of the corresponding mutant proteins. CONCLUSIONS: Although variant alleles of the rod and cone NCKX genes were found, none could be definitively associated with a specific retinal disease. The human phenotype associated with mutant exchanger alleles remains unknown.

Alleles↗