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  • diabetic retinopathy  (2)
  • Keywords Diabetic retinopathy  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Keywords Diabetic retinopathy ; leucocyte ; adhesion ; angiogenesis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p 〈 0.001; p 〈 0.001) particularly those with retinopathy (p 〈 0.001; p 〈 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p 〈 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p 〈 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p 〉 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p 〈 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p 〈 0.01) in particular in those with retinopathy (p 〈 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis. [Diabetologia (1997) 40: 1166–1171]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glucose transport ; diabetic retinopathy ; GLUT 3 ; aldose reductase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The regulation of GLUT-3 and aldose reductase mRNA in retinal endothelial cells and retinal pericytes was studied in response to variations in the extracellular concentration of hexoses. In physiological concentrations of glucose (5 mmol/l), an increase in the level of GLUT-3 mRNA was observed in cultured cells compared to the level of mRNA found in the absence of glucose. In contrast, there was little change in the level of GLUT-3 mRNA when the cells were cultured in the presence of 5 mmol/l galactose. In high concentrations of glucose, there was a decline in GLUT-3 mRNA indicating that the GLUT-3 mRNA is regulated by the extracellular concentration of glucose. In contrast, at both 5 mmol/l and 25 mmol/l glucose, the level of aldose reductase mRNA was increased. Furthermore, there were differences in the magnitude of the increase of aldose reductase mRNA between bovine retinal pericytes and bovine retinal endothelial cells with a greater increase being observed in the pericytes. We propose that this demonstration of a facultative glucose transporter system within retinal cells, and in particular the specific response to different hexoses and the known distinct kinetic parameters of the transporter system in specific cell types, highlights the heterogeneity of hexose transport mechanisms in retinal cells. Thus, hypergalactosaemia as a model system for the study of diabetic retinopathy should be used with caution.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Retina ; angiogenesis ; growth factors ; ischaemia ; diabetic retinopathy ; monocarboxylate transporter type 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The growth of retinal vessels is associated with a number of disease conditions, including diabetic retinopathy and proliferative vitreo-retinopathy. In this study we describe a model of human retinal angiogenesis and show how this may be used to explain the mechanisms that are associated with the growth of new retinal vessels. Methods. A 4 mm diameter disc of retinal tissue was placed within a fibrin matrix and the appearance was monitored daily by light microscopy. Immunohistochemical techniques were used for the detection of, glial fibrillary acidic protein, CD68, the Ki-67 antigen, vascular endothelial growth factor, monocarboxylate transporter type 1 and von Willebrand's factor. Results. Vessels were evident extending from the periphery of the explant and the activation of endothelial cells was shown by immuno-peroxidase staining of paraffin embedded sections of the explants for the expression of the Ki-67 antigen, a marker of cell proliferation. The expression of glial fibrillary acidic protein and von Willebrand's factor increased with duration in culture and the presence of activated macrophages or microglia or both was shown by positive immunoreactivity for CD68 and Ki-67 and were identified by day 3. The presence of endogenous vascular endothelial growth factor and the activation of monocarboxylate transporter type 1 by vascular endothelial growth factor, showed the involvement of specific growth factors. Conclusion/interpretation. The explant model provides evidence for the involvement of macrophages and glial fibrillary acidic protein activation in human retinal angiogenesis and for the expression of monocarboxylate transporter type 1, which is likely to be important in the use of lactate in the hypoxic retina. [Diabetologia (1999) 42: 870–877]
    Type of Medium: Electronic Resource
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