Alteration in Blood Flow in the Pathogenesis of Diabetic Retinopathy

Little, Hunter L.; Sacks, Alvin H.

doi:10.1007/978-94-010-1573-8_70

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…related to the differences, but rather that the abnormalities were associated with the type of diabetes. The raised V1IIR:Ag in our diabetics with retinopathy confirms previous reports (7,3840) as does the raised fibrinogen (25,41,42) being highest in insulin treated diabetics with severe retinopathy. The extent to which abnormalities of platelets as reported here or of platelet function previously described can be considered to be secondary to vascular pathology remains to be clarified but it would appear that therapeutic initiatives in diabetic retinopathy may well be directed primarily towards the endothelial cell rather than modifying platelet behaviour.…”

Section: Discussionsupporting

confidence: 91%

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

et al. 1983

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SummaryTwenty control subjects, 12 insulin treated and 10 non-insulin treated diabetics were studied. All diabetics had retinopathy documented by fluorescein angiography and fluorophotometry. Factor VUIRiAg and plasma fibrinogen concentrations were elevated in both diabetic groups, but more so in the insulin treated patients. Within this latter group the plasma fibrinogen was also correlated with the degree of retinopathy.Platelets separated on linear isosmolar Percoll gradients showed an increase in intraplatelet βTG content and concentration and a slight increase in volume of the lightest platelets in the insulin treated diabetics. Plasma platelet factor 4 and antithrombin III concentrations were normal and plasma βTG levels were elevated only in those patients with renal insufficiency. Platelet aggregometry was performed in 18 diabetic subjects and found to be normal.It is concluded that abnormalities of coagulation and platelets in diabetes are determined by metabolic factors rather than the severity of microvascular disease per se.

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Section: Discussionsupporting

confidence: 91%

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

et al. 1983

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“…3,4 What leads to the occlusion and nonperfusion of retinal capillaries in the early stages of DR (background DR) remains unknown. 4,5 Some authors [6][7][8][9] have attributed a role to increased venous blood flow and impaired autoregulation in the diabetic retinal vasculature and have suggested that the resulting increase in shear stress in the microvasculature, combined with endothelial dysfunction and platelet aggregation, is responsible. Others 7,[10][11][12][13][14] have allocated a role to endothelial and leukocyte activation resulting in leukocyte adhesion, leukostasis, and subsequent capillary closure.…”

mentioning

confidence: 99%

Endothelial Cell Hypertrophy Induced by Vascular Endothelial Growth Factor in the Retina

Hofman

Blijswijk²,

Gaillard³

et al. 2001

Arch Ophthalmol

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To investigate the mechanism leading to capillary nonperfusion of the retina in a monkey model of vascular endothelial growth factor A (VEGF)-induced retinopathy in which capillary closure occurs in a late stage after VEGF treatment.Methods: Two monkeys received 4 intravitreous injections of 0.5 µg of VEGF in one eye and of phosphatebuffered saline in the other eye and were killed at day 9. After perfusion and enucleation, retinal samples were snap frozen for immunohistochemical analysis with the panendothelial cell marker CD31 or were fixed for morphometric analysis at the light and electron microscopic level.Results: At the light microscopic level, all capillaries in the retina of VEGF-injected eyes displayed hypertrophic walls with narrow lumina. In a quantitative analysis of the deep capillary plexus in the inner nuclear layer, VEGF-injected eyes had a significant 5-to 7-fold decrease in total capillary luminal volume. CD31 staining showed that this decrease was not accompanied by a change in the number of capillaries. Electron microscopy revealed that the luminal volume of individual capillaries of the inner nuclear layer of VEGF-injected eyes was significantly decreased due to a 2-fold hypertrophy of the endothelial cells.Conclusions: Luminal narrowing caused by endothelial cell hypertrophy occurs in the deep retinal capillary plexus in VEGF-induced retinopathy in monkeys. This suggests a causal role of endothelial cell hypertrophy in the pathogenesis of VEGF-induced retinal capillary closure. A similar mechanism may operate in retinal conditions in humans associated with ischemia and VEGF overexpression.Clinical Relevance: Capillary nonperfusion occurs in diabetic retinopathy and other ischemic diseases associated with overexpression of VEGF. In addition, VEGFinduced endothelial cell hypertrophy may be causative for capillary closure in these diseases.

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“…Diabetics, compared with healthy controls, show elevated blood viscosity at both high55 56 and low57 58 shear rates, the latter being particularly so in patients with microangiopathy. Hyperviscosity, as in intermittent claudicants, may again be a consequence of the increased plasma level of large molecular weight proteins (fibrinogen, haptoglobin, and x2-macroglobulin)56 59 which enhance red cell aggregation.60 61 A reduction in erythrocyte deformability, as measured by membrane filtration5658 and micropipette elastimetry,62 has also been found, however, particularly in patients with diabetic complications.58 Poor metabolic control reduces erythrocyte deformability,56 and this may be causally related to the cell level of -glycolysated haemoglobin (Hb Al,) which is hyperviscous62 and binds to the cell membrane so that elasticity is reduced. 63 In addition, since 2,3-diphosphoglycerate binds less readily to Hb Aie,64 there is a consequential increase in haemoglobin oxygen affinity and thus in haematocrit and whole-blood viscosity.…”

Section: Diabetic Microangiopathymentioning

confidence: 99%

Blood rheology.

Stuart¹,

Kenny²

1980

J Clin Pathol

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Rheology, the science of the deformation and flow of matter, has become of considerable interest to haematologists, and now the measurement of blood and plasma viscosity is a familiar part of the investigation of vascular disorders and the paraproteinaemias. Developments in instrumentation have led to the measurement of plasma viscosity and the zeta sedimentation ratio as practical alternatives to the erythrocyte sedimentation rate, and a variety of methods have also been introduced for the study of red cell deformability. It is therefore an appropriate time to review these recent developments and to examine their potential application to the investigation and management of clinical disorders. Determinants of viscosityAll fluids resist, to a greater or lesser extent, attempts to alter their shape, and this resistance to flow is a measure of a fluid's viscosity. During flow, as layers of fluid move parallel to one another at different rates, a velocity gradient forms between these layers and is known as the shear rate; it is measured in reciprocal seconds (s-1). The force required to produce this velocity gradient is the shear stress and is measured in newtons per square metre (NM-2). Viscosity can now be redefined as the ratio of shear stress to shear rate, the unit of viscosity being the pascal second (Pa s; conversion factor -1 mPa s = 1 centipoise).Simple fluids, such as plasma and most oils, show a linear relationship between shear stress and shear rate (Newtonian behaviour) so that the viscosity remains constant. Whole blood, however, behaves as a non-Newtonian fluid in that viscosity increases exponentially at the low shear rates (below 50 s-1) that characterize venous flow. This increase is due to the larger molecular weight plasma proteins (fibrinogen and certain globulins) which overcome the zeta potential between erythrocytes and form rouleaux; these large cellular aggregates cause a disproportionate increase in viscosity. At shear rates below 1 s51, alterations in plasma fibrinogen around the upper limit ofthe physiological range have a pronounced

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Alteration in Blood Flow in the Pathogenesis of Diabetic Retinopathy

Cited by 5 publications

References 9 publications

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

Platelets, Coagulation and Fibrinolysis in Patients with Diabetic Retinopathy

Endothelial Cell Hypertrophy Induced by Vascular Endothelial Growth Factor in the Retina

Blood rheology.

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