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Biomedical subjects

E M Kohner

Publications and source records attributed to E M Kohner.

At least 55 records · Page 3Linked to original sources
PubMed1993

A study of the effects of human blood derivatives and individual growth factors on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells.

Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [3H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED50 = 1.8 x 10(-13) mol/l), acidic fibroblast growth factor (7.4 x 10(-12) mol/l), insulin-like growth factor 1 (8.6 x 10(-10) mol/l), insulin (158 microU/ml) and endothelin-1 (6.1 x 10(-10) mol/l). Transforming growth factor beta 1 inhibited DNA synthesis (ID50 = 3.6 x 10(-10) mol/l) and so did heparin (1.4 x 10(-6) mol/l) and low molecular weight heparin (2.9 x 10(-6) mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2 x 10(-13) mol/l) and acidic fibroblast growth factor (1.3 x 10(-9) mol/l), and inhibited by transforming growth factor beta 1 (1.6 x 10(-12) mol/l). Neither cell type was stimulated by platelet-derived growth factor (A + B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pericyte mitogenic activity is reduced in the blood of type 1 diabetic patients with and without retinopathy.

Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with long-term type 1 (insulin-dependent) diabetes and no retinopathy differ from those with retinopathy and/or non-diabetic controls in their ability to stimulate DNA synthesis in cultured bovine retinal pericytes and endothelial cells. As a general trend, whole blood serum, platelet-rich plasma and platelet-free plasma from patients without and with retinopathy stimulated thymidine incorporation in both cell types less than derivatives from controls. Serum, 0.1% v/v final concentration in culture medium, from patients without retinopathy was less active (114.5 +/- 24.5% of a standard stimulus produced by 0.1% fetal calf serum) than that from patients with the complication (132.6 +/- 20.8%, P = 0.003) and both were less potent than control sera (143.6 +/- 28.0%, P < 0.001 and P = 0.013, respectively). Lack of support from circulating factor(s) may contribute to the disappearance of pericytes from the capillary wall in diabetes but further investigations are necessary to clarify the mechanisms that prevent the development of microangiopathy in some patients.

Adult↗
PubMed1993

The effect of acetazolamide on the retinal circulation.

The effect of the carbonic anhydrase inhibitor, acetazolamide, on the retinal circulation was studied in 10 healthy volunteers. Acetazolamide was administered intravenously at a dose of 500 mg. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and vessel diameter measurement using computerised digital image analysis of monochromatic fundus photographs. There was a significant increase in retinal blood flow at 30 minutes and 60 minutes after acetazolamide injection (p = 0.002). Retinal vessels showed vasodilatation reaching significant levels 60 minutes after the injection (p < 0.03). An increase in red cell velocity was observed at 30 and 60 minutes (p < 0.002). A significant reduction in intraocular pressure occurred at 30 and 60 minutes after the injection (p < 0.001). The mechanisms responsible for the increase in retinal blood flow acted via significant increases in perfusion pressure (p < 0.05), red cell velocity (p < 0.002) and retinal vessel dilatation (p < 0.03). An increase in tissue PCO2 and a reduction in pH are thought to be responsible for the vascular dilatation. The increase in retinal blood flow with acetazolamide may serve to limit optic disc and retinal ischaemia in acute glaucoma and central retinal artery occlusion respectively.

Acetazolamide↗
PubMed1993

The effect of diabetic control on diabetic retinopathy.

Poor diabetic control is associated with an increased risk of diabetic retinopathy, and there is a particularly increased risk in insulin-dependent (type 1) patients for the development of proliferative diabetic retinopathy. There is good evidence that hyperperfusion is an important factor in the evolution of diabetic retinopathy. This hyperperfusion is worse in those with poor diabetic control. The increased blood flow associated with high glucose interferes with autoregulation, and this further increases flow, damaging the endothelial lining of the blood vessels and leading to worsening of the retinopathy.

Blood Flow Velocity↗
PubMed1992

Retinal vessel measurement: comparison between observer and computer driven methods.

A method of semi-automated image analysis for the measurement of retinal vessel diameters is described. This was compared with an observer-driven method for reproducibility and accuracy. The coefficient of variation for the data from the semi-automated method was 1.5-7.5% (depending on the vessel diameter) compared to 6-34% with the observer-driven method. The mean vessel diameters using the observer-driven method tended to be higher; however, this did not reach significance. The speed and low inter- and intra-observer variability for the semi-automated method make it a useful technique for measuring retinal blood vessel diameters. A larger variability was found between photographs taken at different times. This may be due to changes in retinal vessel diameter with changes in retinal perfusion pressure during the cardiac cycle.

Diabetic Retinopathy↗
PubMed1992

Validation and reproducibility of bidirectional laser Doppler velocimetry for the measurement of retinal blood flow.

Bidirectional laser Doppler velocimetry (BLDV) for the measurement of retinal blood flow was validated in six anaesthetised minipigs, by comparing BLDV derived results with those obtained using radioactively labelled microspheres (RLM). The mean velocity of blood (Vmean) was calculated from the maximum red blood cell velocity measured by BLDV. Volumetric flow rate was determined from Vmean and vessel diameter, measure from monochromatic fundus photographs. Total retinal blood flow (TRBF) was calculated by summating flow values obtained for each retinal vein draining into the optic disc. A significant correlation was found between the TRBF results obtained by the two techniques (r = 0.99, p less than 0.001). The BLDV results were between 3-35 microliters/min lower than the corresponding RLM results (p = 0.05). Values of 57 +/- 24 microliters/min and 76 +/- 34 microliters/min were obtained for TRBF using the BLDV and RLM techniques respectively. Reproducibility studies with BLDV were also performed in six anaesthetised pigs over three hours and in six normal human volunteers over two hours and two weeks. No significant difference between measurements was found with time. Ninety five percent confidence limits of +/- 9.8% for the six pigs and +/- 8.9% for the six human volunteers were found for measurements on the same day and at two weeks. We conclude that with a sample size of six, changes in flow of approximately 20% can be detected using BLDV and monochromatic fundus photography.

Adult↗
PubMed1992

The renin-angiotensin system and diabetic retinopathy.

The importance of the renin-angiotensin system in the eye has not been clearly established, nor is it known whether it is of importance in the evolution of diabetic retinopathy. Circulating renin is produced in the kidney and other tissues; its main importance is in the control of blood pressure. Elevated levels have been found in diabetic patients with microvascular complications. There is also some suggestion that the prorenin content is elevated in diabetics and that this is an indicator of the development of microvascular complications in the next few years. Angiotensin-converting enzyme (ACE) inhibitors have been found to reduce the leakage in early diabetic retinopathy, but it is possible that this was only due to a reduction of blood pressure. Angiotensin II was found to induce neovascularisation in corneal pocket experiments, and the replication of aortic endothelial cells has been reported. We were unable to find any increased replication of retinal endothelial cells treated with angiotensin II. It is possible that the main function of the renin-angiotensin system in the eye is the regulation of local blood flow.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Characterization of release of basic fibroblast growth factor from bovine retinal endothelial cells in monolayer cultures.

Release of basic fibroblast growth factor (bFGF) was investigated in bovine retinal endothelial cells (BREC) maintained in monolayer culture. Confluent cells released bFGF into serum-free culture medium or medium containing 5% serum at rates of up to 105.2 and 61.3 pM/day respectively. bFGF release coincided with a decrease in monolayer cell number and increases in lactate dehydrogenase (LDH) concentration and cells and cell-debris particles in the medium, which suggested that cell damage and lysis were responsible for growth-factor release. Maximum bFGF release at 24 h (230 +/- 10 pM) occurred when the cells were treated with lipopolysaccharide (10 micrograms/ml), which also produced the greatest changes in parameters of cell damage. Sub-confluent cells showed little overt damage at 24 h, but released bFGF (78 +/- 20 pM) along with LDH, indicating that some cell lysis had occurred. Insulin-like growth factor 1 (IGF-1) was also released into serum-free culture medium at a rate of 0.34 nM/day, but not into medium containing serum or when the cells were treated with lipopolysaccharide. This implies that the mechanism of IGF-1 release is different from that of bFGF and is not related to cell damage. Culture medium conditioned by BREC stimulated the proliferation of these cells, as measured by an increase in their incorporation of [methyl-3H]thymidine from 7550 +/- 479 to 10467 +/- 924 d.p.m. These results demonstrate that bFGF is released from damaged BREC and that medium conditioned by these cells can stimulate retinal-endothelial-cell proliferation. This strengthens the case for an involvement of this growth factor in retinal neovascularization.

Animals↗
PubMed1991

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Animals↗
PubMed1991

Effect of meal on retinal blood flow in IDDM patients.

OBJECTIVE: The effect of postprandial hyperglycemia on retinal blood flow was examined in 11 adults with insulin-dependent diabetes mellitus (IDDM) and 9 nondiabetic subjects. RESEARCH DESIGN AND METHODS: Retinal blood flow was measured with bidirectional laser Doppler velocimetry before and 60 and 120 min after a 50-g carbohydrate breakfast. Diabetic subjects were studied twice, being randomized to take their usual insulin (isoglycemic study) or to omit their morning short-acting insulin (hyperglycemic study). Nondiabetic subjects were studied once and received no insulin. RESULTS: Plasma glucose rose significantly (from 11.5 +/- 5.2 to 22.1 +/- 5.5 mM, P less than 0.001) during the hyperglycemic study but not during the isoglycemic or nondiabetic studies. There were no significant changes in blood pressure or retinal blood flow in any of the groups studied. CONCLUSIONS: Short-term hyperglycemia does not increase retinal blood flow.

Blood Glucose↗
PubMed1990

A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig.

The effect of acute hypoglycaemia (plasma glucose less than 2.2 mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (+/- 2.8 SEM) microliters/min to 29.7 (+/- 7.5) microliters/min during hypoglycaemia (p less than 0.05) with a return to 18.6 (+/- 3.6) microliters/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences.

Animals↗
PubMed1990

Macular blood flow response to acute reduction of plasma glucose in diabetic patients measured by the blue light entoptic technique.

The response of retinal blood flow to acute reduction in plasma glucose levels was studied in 20 poorly controlled type I diabetic patients. Perifoveal flow velocity was determined, using the blue-light entoptoscope, and arterial calibers measured, using a computer-aided digitizing system. Mean plasma glucose level was lowered from 17.7 +/- 4 to 7.0 +/- 1 mmol/l after a subcutaneous insulin infusion and measurements taken at both glucose levels. The autoregulatory change induced by breathing 60% oxygen at the two plasma glucose levels also was compared. Mean flow velocities were 0.54 +/- 0.28 mm/sec at a high plasma glucose level compared with 0.55 +/- 0.32 mm/sec at a low plasma glucose level, whereas hyperoxia reduced these by 16.58 and 16.71%, respectively. No significant difference in the responses of arterial diameters to hyperoxia between the two glucose levels was found. The authors conclude that acute reduction in plasma glucose level in this group of patients is not associated with significant changes in macular blood flow or in alteration in autoregulation.

Adult↗
PubMed1990

Aspects of growth hormone control in diabetes.

Growth Hormone (GH) has been implicated in the development of retinal new vessels that characterise diabetic proliferative retinopathy. Formerly, pituitary ablation was successful in causing such new vessels to regress but this approach has been largely superseded by panretinal photocoagulation. A clearer understanding of the GH abnormalities in diabetes might not only shed light on the process of retinal new vessel formation but could also provide a means for pharmacological suppression of GH in those patients not fully responding to laser photocoagulation. In this review, GH control in diabetes is considered with particular reference to studies in patients with diabetic retinopathy.

Acetylcholine↗
PubMed1990

Hypoxic viscosity and diabetic retinopathy.

Diabetic and sickle retinopathy have features in common--for example, venous dilatation, microaneurysms, and capillary closure preceding neovascularisation. Bearing in mind that haemoglobin in poorly controlled diabetes is abnormal and that extremely low oxygen tensions (known to cause sickling) exist in the healthy cat retina, we wished to explore the possibility that diabetic blood, like that of sickle cell disease, may become more viscous when deoxygenated. To do this we measured whole blood viscosity, under oxygenated and deoxygenated conditions, of 23 normal persons, 23 diabetic patients without retinopathy, and 34 diabetic patients with retinopathy. The shear rate used was 230 s-1, which is similar to that thought to prevail in the major retinal veins. The viscosity of blood from normal persons, corrected for packed cell volume, did not change significantly on deoxygenation: mean 4.54 (SD 0.38) cps, versus, 4.57 (0.39) paired t test, p = 0.66. Similarly the blood from diabetics without retinopathy showed no change: 4.42 (0.45) versus 4.42 (0.30), p = 0.98; whereas the blood from patients with retinopathy changed from 4.82 (0.48) to 4.95 (0.63), p = 0.027. The hypoxic viscosity ratio (deoxygenated divided by oxygenated viscosity) correlated with total serum cholesterol (r = 0.44, p = 0.018) but not with HbA1, serum glucose, triglycerides, or age. A disproportionate increase in venous viscosity relative to arterial viscosity would lead to increased intraluminal and transmural pressure and therefore exacerbate leakage across capillary walls.

Adult↗