Biomedical subjects

Geoffrey B Arden

Publications and source records attributed to Geoffrey B Arden.

7 recordsLinked to original sources

PubMed2006

Light and alcohol evoked electro-oculograms in cystic fibrosis.

Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) which is a chloride channel. CFTR is expressed in the retinal pigment epithelium (RPE) where it is believed to be important in generating the fast oscillations (FOs) and potentially contributing to the light-electro-oculogram (EOG). The role of CFTR in the alcohol-EOG is unknown. We recruited six individuals with CF (three homozygotes for Delta508 and three heterozygous for Delta508) and recorded the light- and alcohol-EOGs as well as the FOs and compared them to a control group. The results showed that in the CF group the amplitude of the alcohol- and light-EOGs were normal. However, the time to peak of the light- and alcohol-rises were significantly faster than in the control group. We conclude that CFTR is not primarily responsible for the alcohol- or light-rises but is involved in altering the timing of these responses. The FOs showed differences between the homozygotes, heterozygotes and the controls. The amplitudes were significantly higher and the time to the dark troughs were significantly slower in the heterozygote group compared to both controls and the homozygotes. In contrast, the homozygotes did not differ in either amplitude or the timing of the FOs compared to the controls.

Adaptation, Ocular↗

PubMed2006

P-Glycoprotein expression in human retinal pigment epithelium cell lines.

P-Glycoprotein (P-gp), an active efflux transporter encoded by the MDR1 gene, has recently been identified in the human and pig retinal pigment epithelium (RPE) in situ. Efflux pumps such as P-gp are major barriers to drug delivery in several tissues. We wished to establish whether human RPE cell lines express P-gp under the culture conditions recommended for each cell line so as to determine their suitability as in vitro models for predicting drug transport across the outer blood-retinal barrier. Three human RPE cell lines, ARPE19, D407 and h1RPE were investigated. Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to determine the expression of MDR1 mRNA. Immunocytochemistry using the P-gp-specific antibody C219 was undertaken to investigate the presence of P-gp protein in each cell type. Uptake of rhodamine 123, a P-gp substrate, in the presence or absence of pre-treatment with a P-gp inhibitor, verapamil, was measured in each cell line to determine functional expression of P-gp. For all experiments, MDCK cells stably transfected with the human MDR1 gene (MDCK-MDR1) were used as a positive control. ARPE19 cells were consistently negative for P-gp as assessed by RT-PCR and immunocytochemistry. By contrast, RT-PCR of D407 and h1RPE samples yielded weak bands corresponding to MDR1; P-gp protein expression, as demonstrated by C219 immunoreactivity, was also present. Rhodamine uptake after treatment with verapamil was significantly greater in D407 and MDCK-MDR1, indicating functional expression of P-gp in these two cell lines. No evidence of functional P-gp was found in ARPE19 and h1RPE. In conclusion, D407 and h1RPE cells express P-gp, though functional activity was demonstrable only in D407 cells. ARPE19 cells do not express P-gp. Of these human RPE cells lines D407 could be considered as a suitable model for in vitro drug transport studies, particularly those involving P-gp substrates, without modification of their usual culture conditions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

The electro-oculogram.

The retinal pigment epithelium (RPE) lying distal to the retina regulates the extracellular environment and provides metabolic support to the outer retina. RPE abnormalities are closely associated with retinal death and it has been claimed several of the most important diseases causing blindness are degenerations of the RPE. Therefore, the study of the RPE is important in Ophthalmology. Although visualisation of the RPE is part of clinical investigations, there are a limited number of methods which have been used to investigate RPE function. One of the most important is a study of the current generated by the RPE. In this it is similar to other secretory epithelia. The RPE current is large and varies as retinal activity alters. It is also affected by drugs and disease. The RPE currents can be studied in cell culture, in animal experimentation but also in clinical situations. The object of this review is to summarise this work, to relate it to the molecular membrane mechanisms of the RPE and to possible mechanisms of disease states.

Animals↗

PubMed2004

Two components of the human alcohol electro-oculogram.

Light onset or drinking alcohol causes the standing potential of the eye to rise and then fall to a trough (the EOG). After allowing for the time for the alcohol to be absorbed into the blood stream, the changes of current with time are identical for the two agents but each acts through a separate pathway, on the same effector mechanism. We have shown that +ve and -ve processes of the alcohol-EOG may be differentially affected in disease. We have now determined the separate dose-response relationship of the two voltage changes. Alcohol diluted with water was given by mouth to fasting dark-adapted subjects. Recordings continued until both the positive peak and the later negative trough were well-characterised. Doses of alcohol ranged from 3.54 to 450 mg Kg(-1) of body weight. Experiments were carried out on three normal subjects, 4-8th decade. The results are consistent with the hypothesis that each voltage change is determined by the relation: [EtOH] x [R] <--> [EtOH.R], where <--> represents a reversible reaction. For the +ve peak, semi-saturation occurs at approximately 35 mg Kg(-l). For the -ve trough it is smaller, 11 mg Kg(-l). Therefore the result is consistent with there being 2 distinct processes, and the human EOG cannot be a single 'damped oscillation'. During the short period when change of blood alcohol concentration is effective in causing the EOG sequence (using doses which provoke large voltage changes), the computed blood concentration varies from 0.01 to 0.1 mM, i.e. is > 2 orders of magnitude less than the levels required for intoxication.

Administration, Oral↗

PubMed2004

The multifocal pattern electroretinogram in glaucoma.

BACKGROUND: The pattern ERG can be used to detect early glaucomatous change, because the response of cells in the inner retina from (typically) 20 degrees -40 degrees of area is reduced before perimetric abnormality is certain. The multifocal pattern electroretinogram (mfPERG) allows analysis of many local regions within this area. The aim of this study was to investigate whether in patients with presumed glaucoma the mfPERG permits diagnosis and discrimination from normals. METHODS: Measurements on 25 age-related normal eyes were compared to those on 23 eyes with different stages of glaucoma. A RETIScan system was used to generate a stimulus pattern of 19 hexagons, each consisting of six triangles. The triangles pattern-reversed black to white at 75 Hz. Those 19 hexagons were grouped into three stimulus regions: a central field, a middle, and a peripheral ring. The complete array subtended 48 degrees at the eye. The hexagons alternated between black and white, in a temporal pattern that followed a corrected binary m-sequence (length 512, 10 cycles with 39 s each). The amplitudes and latencies of positive responses at approximately 50 ms (P-50) and negative responses at approximately 95 ms (N-95) were analyzed. RESULTS: In patients with glaucoma the P-50 and N-95 components of the mfPERG were significantly reduced for the central area and both outer rings compared to normal volunteers (p<0.001, Mann-Whitney-U). The most distinct reduction was observed for N-95 and the central ring. Changes in latencies were not conclusive. The reduction of the components increased with the stage of glaucoma. A predictive model for detecting early glaucomatous changes was designed based on P-50-N-95 with 88% sensitivity and 76% specificity. CONCLUSION: In glaucoma a marked reduction of components, especially centrally is observed in the mfPERG. This hints to an early involvement of central ganglion cells and may be useful for future functional tests.

Adult↗

PubMed2003

Differential effects of light and alcohol on the electro-oculographic responses of patients with age-related macular disease.

PURPOSE: Alcohol (EtOH) affects the electro-oculogram (EOG) in ways very similar to light, although the two agents act on the RPE through different routes. Are the EOGs to light and to alcohol affected similarly in age-related macular degeneration (AMD) and age-related maculopathy (ARM)? METHODS: Standard eye movements and recording of EOGs were used. After 26 minutes of baseline recording in darkness, subjects were either exposed to 30 cd/m(2) light or drank 226 mg/kg alcohol (7.1% vol/vol) in water. RESULTS: In 17 patients with ARM and AMD (aged 67-86 years; mean, 77), the light-EOG was slowed in comparison to normal, and the voltage changes were somewhat reduced. The mean reduction in the alcohol-EOG (EtOH-EOG) was much greater. The reduction was equal in the two eyes, regardless of uniocular foveal impairment. Some EtOH-EOG loss occurred in patients with minor fundus changes and no loss of acuity, but the loss was greater in patients with "wet" or "dry" ARM and AMD. Grading of RPE changes correlated with the decrease in EtOH-EOG responsiveness, but not with light-EOG responsiveness. CONCLUSIONS: EtOH- and light-EOGs are affected differentially. In ARM, even with minor fundus changes, patients appear to have a general abnormality in the RPE. The alcohol response abnormality is correlated to the fundus appearance, but not with age. These results provide further evidence that EtOH acts by a pathway different from that governing the action of light. These results support histologic and other evidence that in ARM there is a functional barrier between the choroid and the RPE-retina.

Adult↗

PubMedDate not supplied

The multifocal pattern electroretinogram in chloroquine retinopathy.

PURPOSE: Optimal screening for ocular toxicity caused by chloroquine and hydroxychloroquine is still controversial. With the multifocal pattern electroretinogram (mfPERG), a new electrophysiological technique has recently become available to detect early changes of ganglion cells. In this study this new technique is applied to a series of 10 patients seen consecutively receiving long-term chloroquine medication. METHODS: In 10 patients receiving chloroquine medication, clinical examination, Amsler visual field testing and computerized color vision testing were performed. If toxicity was suspected, automated perimetry was carried out. In addition, in all patients conventional pattern electroretinogram (PERG) and mfPERG testing were performed. RESULTS: On clinical examination 8 patients showed no chloroquine-associated maculopathy, while 2 patients did. Of these 2, only 1 reported abnormalities when viewing the Amsler chart, while automated perimetry showed typical, ring-like paracentral scotomas in both affected patients and color vision was significantly abnormal. In the normal patients, 4 of 8 had a mild color vision disturbance, which correlated to age-related macular changes. The amplitudes of the PERG and the central (approximately 10 degrees ) responses of the mfPERG were markedly reduced in chloroquine maculopathy, while the latencies were unchanged. The peripheral rings of mfPERG (ranging to 48 degrees ) were not affected by chloroquine toxicity. Both PERG and mfPERG were less affected by age-related macular changes. CONCLUSIONS: The reduction of PERG and central mfPERG responses in chloroquine maculopathy may help with the early detection of toxicity.

Adult↗