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  • 1
    ISSN: 1432-0428
    Keywords: Obese fa/fa rat ; non-insulin-dependent diabetes ; oral glucose tolerance ; diabetic microangiopathy ; retinal capillary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetically obese fatty (fa/fa) male rats with abnormal oral glucose tolerance associated with initial hyperinsulinaemia as well as control lean (FA/FA) rats were investigated for the development of retinal microangiopathies. The animals were kept on a standard or sucrose supplemented diet. When tested at 60 weeks, the glucose intolerance of fa/fa rats was accompanied by an insulin response that was now either comparable to that of lean rats (standard diet) or close to nil (sucrose supplemented diet). At killing (68 weeks of age), retinal vasculature was examined by electron microscopy and morphological changes were quantitatively assessed by ultrastructural morphometry. A retinal microangiopathy was observed in all mutant animals which was more pronounced in the sucrose fed group, and which was characterized by: (1), an increase in focal thickenings and in nodules of the basement membrane adjacent to the perivascular glial cells; (2), a decrease in the number of pericyte nulei with concomitant signs of early degenerative cytoplasmic changes of pericytes; (3), an increase in the pinocytic activity of endothelial cells, indicative of presumptive changes in vascular permeability; (4), an increase in the number of intercellular endothelial junctions; (5), the presence of numerous stimulated platelets within capillaries. The fa/fa rat may thus be considered as a suitable model for studying the pathophysiology of ocular complications, in particular retinopathy accompanying non-insulin-dependent diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Diabetic retinopathy ; Endothelium ; Growth factors ; Pericytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with longterm 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 andP=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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Diabetic retinopathy ; Endothelial cells ; Growth factors ; Pericytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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= 1.8×10−13 mol/l), acidic fibroblast growth factor (7.4× 10−12 mol/l), insulin-like growth factor 1 (8.6×10−10 mol/l), insulin (158 μU/ml) and endothelin-1 (6.1×10−10 mol/l). Transforming growth factor β1 inhibited DNA synthesis (ID50=3.6×10−10 mol/l) and so did heparin (1.4×10−6 mol/l) and low molecular weight heparin (2.9×10−6 mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2×10−13 mol/l) and acidic fibroblast growth factor (1.3×10−9 mol/l), and inhibited by transforming growth factor β1, (1.6×10−12 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. Some, though, may play a role in the regulation of pericyte turnover through paracrine mechanisms which should be further investigated.
    Type of Medium: Electronic Resource
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