Biomedical subjects

Louvenia Carter-Dawson

Publications and source records attributed to Louvenia Carter-Dawson.

6 recordsLinked to original sources

PubMed2005

Scaling the structure--function relationship for clinical perimetry.

PURPOSE: The full ranges of glaucomatous visual field defects and retinal ganglion cell losses extend over several orders of magnitude and therefore an interpretation of the structure-function relationship for clinical perimetry requires scaling of both variables. However, the most appropriate scale has not been determined. The present study was undertaken to compare linear and logarithmic transformations, which have been proposed for correlating the perimetric defects and neural losses of glaucoma. METHODS: Perimetry, by behavioural testing, and retinal histology data were obtained from rhesus monkeys with significant visual field defects caused by experimental glaucoma. Ganglion cell densities were measured in histologic sections of retina that corresponded to specific perimetry test locations for the treated and control eyes. The linear (percentage) and logarithmic (decibel) relationships for sensitivity loss as a function of ganglion cell loss were analysed. RESULTS: With decibel scaling, visual sensitivity losses and ganglion cell densities were linearly correlated with high coefficients of determination (r(2)), although the parameters of the functions varied with eccentricity. The structure-function relationships expressed as linear percentage-loss functions were less systematic in two respects. Firstly, the relationship exhibited considerable scatter in the data for small losses in visual sensitivity and, secondly, visual sensitivity losses became saturated with larger losses in ganglion cell density. The parameters of the percentage-loss functions also varied with eccentricity, but the variation was less than for the decibel-loss functions. CONCLUSIONS: Linear scaling of perimetric defects and ganglion cell losses might potentially improve the structure-function relationship for visual defects associated with small amounts of cell loss, but the usefulness of the relationship is limited because of the high variability in that range. With log--log co-ordinates, the structure--function relationship for clinical perimetry is relatively more accurate and precise for cell losses greater than about 3 dB. The comparatively greater accuracy and precision of decibel loss functions are a likely consequence of the logarithmic scale of stimulus intensities for perimetry measurements and because the relationship between visual sensitivity and the number of neural detectors is a form of probability summation.

Animals↗

PubMed2004

Glutathione content is altered in Müller cells of monkey eyes with experimental glaucoma.

Extracellular levels of glutamate are thought to be increased in glaucoma and thus contribute to retinal damage. An increase in glutamate concentration or duration in the extracellular retinal space is expected to impact glutathione content in Müller cells since glutamate is the rate-limiting constituent in glutathione synthesis. We have investigated whether glutathione content is changed in retinal Müller cells of monkeys with experimental glaucoma using immunocytochemistry and image analysis. Müller cells in glaucomatous retinas showed significantly greater immunoreactivity (27-57%) for glutathione than those in fellow control retinas, increasing with the duration of elevated intraocular pressure (IOP). This pattern of labeling was prominent in all four monkeys studied. The presence of more glutathione in Müller cells of glaucomatous retinas is consistent with an increase in extracellular glutamate and an increase in transport and metabolism of glutamate.

Animals↗

PubMed2004

Neural losses correlated with visual losses in clinical perimetry.

PURPOSE: The validity of clinical perimetry for evaluation of the pathology of glaucoma is based on correlated losses in retinal ganglion cells and visual sensitivity, but procedures to quantify neural losses from visual field defects have not been developed. The purpose of the present study was to investigate the neural and sensitivity losses from experimental glaucoma to establish the framework for a quantitative model for the structure-function relationships of standard clinical perimetry. METHODS: Perimetry, by behavioral testing, and retinal histology data were obtained from rhesus monkeys with significant visual field defects caused by experimental glaucoma. Ganglion cell densities were obtained from sections of retina that corresponded to 16 perimetry test locations. Perimetry sensitivity as a function of ganglion cell density at corresponding retina/visual field locations was analyzed. RESULTS: The structure-function relationships were linear on log-log coordinates, with parameters that varied systematically with eccentricity. The slope value varied from 1.25 dB/dB at 4.2 degrees from fixation to a value of 2.32 dB/dB at 24 degrees from fixation, whereas the intercept value varied from -25.2 dB to -55.7 dB over the same range of eccentricities. The structure-function relationships produced a model to predict the ganglion cell density underlying a given level of visual sensitivity and location in the visual field. The model, with no free parameters, produced an accurate and relatively precise quantification of retinal ganglion cell losses caused by experimental glaucoma in monkeys. However, because the early detection of glaucoma is limited by intersubject variability, ganglion cell losses of 40% to 50% were necessary before visual sensitivity losses exceeded the normal 95% confidence limits. CONCLUSIONS: With retinal eccentricity as a factor, the neural losses from glaucoma are predictable from visual sensitivity measurements by clinical perimetry. The relationships derived from experimental glaucoma in monkeys also accurately predict the rate of age-related losses of retinal ganglion cells in humans, based on the normative perimetry data for age-related reductions in visual sensitivity. The success of the model in this study suggested that it is potentially applicable to the clinical interpretation of the state of glaucomatous optic neuropathy.

Animals↗

PubMed2002

Visual field defects and neural losses from experimental glaucoma.

Glaucoma is a relatively common disease in which the death of retinal ganglion cells causes a progressive loss of sight, often leading to blindness. Typically, the degree of a patient's visual dysfunction is assessed by clinical perimetry, involving subjective measurements of light-sense thresholds across the visual field, but the relationship between visual and neural losses is inexact. Therefore, to better understand of the effects of glaucoma on the visual system, a series of investigations involving psychophysics, electrophysiology, anatomy, and histochemistry were conducted on experimental glaucoma in monkeys. The principal results of the studies showed that, (1) the depth of visual defects with standard clinical perimetry are predicted by a loss of probability summation among retinal detection mechanisms, (2) glaucomatous optic atrophy causes a non-selective reduction of metabolism of neurons in the afferent visual pathway, and (3) objective electrophysiological methods can be as sensitive as standard clinical perimetry in assessing the neural losses from glaucoma. These experimental findings from glaucoma in monkeys provide fundamental data that should be applicable to improving methods for assessing glaucomatous optic neuropathy in patients.

Animals↗

PubMed2002

Vitreal glutamate concentration in monkeys with experimental glaucoma.

PURPOSE: To investigate the hypothesis that the pathophysiology for the death of retinal ganglion cells in glaucoma involves excitotoxic effects from elevated concentrations of vitreal glutamate. METHODS: Experimental glaucoma was induced in the right eyes of 18 rhesus monkeys by argon laser treatments to the trabecular meshwork. After significant visual field defects and/or typical clinical glaucomatous changes had developed (1.5-13 months), the eyes were removed, and a sample (0.1-0.2 mL) of posterior vitreous was collected. Similar vitreous samples also were collected from eight untreated monkeys. The vitreous samples were analyzed in a masked fashion by high-pressure liquid chromatography in two independent laboratories. Mean levels of vitreal glutamate were determined for the treated and control eyes and differences between groups of eyes were evaluated by Student's t-test. RESULTS: The mean level (+/- SD) of vitreal glutamate in the eight untreated monkeys was 5.0 +/- 2.0 microM. A similar level of 5.7 +/- 1.8 microM was measured in the untreated eyes of monkeys with experimental glaucoma. In the glaucomatous eyes, the mean concentration of vitreal glutamate was 5.7 +/- 2.6 microM, which was not significantly different from the concentrations in the control eyes. CONCLUSIONS: Vitreal glutamate concentrations were not elevated in eyes with anatomic and functional damage from experimental glaucoma. This finding is in contradiction to previous reports that vitreal glutamate increases to toxic levels and probably contributes to glaucomatous damage of retinal ganglion cells.

Amino Acids↗

PubMedDate not supplied

Activation of protein kinase C reduces GLAST in the plasma membrane of rat Müller cells in primary culture.

In this study, a Müller cell culture preparation from young rats was used to investigate the regulation of GLAST transport activity in native cells. Immunohistochemical analysis confirmed GLAST to be the predominant glutamate transporter expressed by the cells through five passages. [3H]-glutamate uptake assays showed the typical Na+-dependent glutamate transport which was blocked by L-(-)-threo-3-hydroxyaspartate (L-THA), a competitive inhibitor. Glutamate transport was decreased significantly in Müller cells exposed to phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator. A similar effect on [3H]-D-aspartate (nonmetabolizable glutamate analog) uptake ruled out the possibility that the decrease was a consequence of altered metabolism. However, PMA did not affect Na+-dependent [3H]-glycine transport, indicating the absence of a nonspecific change in the electrochemical gradients. The PMA effect on glutamate uptake was evidenced by partial blocking with a specific PKC inhibitor, bisindolymaleimide II (Bis II). Activation of PKC did not change the Km, but the Vmax was significantly reduced. Image analysis of Müller cells with biotinylated cell membranes immunolabeled with GLAST shows a reduction of GLAST in the plasma membrane. In conclusion, these data show that rat Müller cells in primary cultures express GLAST and that PKC activation affects GLAST transport activity by decreasing cell surface expression.

Amino Acid Transport System X-AG↗