Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments.

Stitt, Alan W.; Anderson, Heather; Gardiner, Tom; Archer, D. B.

doi:10.1136/bjo.78.2.133

Cited by 70 publications

(39 citation statements)

References 36 publications

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“…Shear stress levels are greatest in retinal arteries and arterioles 67 and during diabetes BM thickening is significantly increased in capillaries that are located proximal to the arterial side of the retinal circulation. 68 Figure 3 A unifying haemodynamic model for the pathogenesis of diabetic retinopathy. Without demonstrating the complexities of metabolic and biochemical pathogenic pathways that superimpose on this model, the purple region shows how early stage hypoperfusion could lead to progressive hypoxia and increased leucocytic adherence to the retinal capillaries.…”

Section: Retinal Capillary Basement Membrane Thickeningmentioning

confidence: 99%

Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Curtis

Gardiner

Stitt

2009

Eye

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318

231

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Retinopathy is a major complication of diabetes mellitus and this condition remains a leading cause of blindness in the working population of developed countries. As diabetic retinopathy progresses a range of neuroglial and microvascular abnormalities develop although it remains unclear how these pathologies relate to each other and their net contribution to retinal damage. From a haemodynamic perspective, evidence suggests that there is an early reduction in retinal perfusion before the onset of diabetic retinopathy followed by a gradual increase in blood flow as the complication progresses. The functional reduction in retinal blood flow observed during early diabetic retinopathy may be additive or synergistic to proinflammatory changes, leucostasis and vasoocclusion and thus be intimately linked to the progressive ischaemic hypoxia and increased blood flow associated with later stages of the disease. In the current review a unifying framework is presented that explains how arteriolar dysfunction and haemodynamic changes may contribute to late stage microvascular pathology and vision loss in human diabetic retinopathy.

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Section: Retinal Capillary Basement Membrane Thickeningmentioning

confidence: 99%

Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Curtis

Gardiner

Stitt

2009

Eye

Self Cite

318

231

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“…In diabetes, capillary endothelial cells and their basement membranes undergo major changes, particularly in the heart [10], retina [11,12], and kidney [13,14,15,16,17,18]. For the nervous tissue, the perineural [19,20,21] and endoneural capillaries [22,23] were reported as getting altered too during diabetes.…”

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confidence: 99%

Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats

Bouchard

Bendayan

2002

Diabetologia

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Aims/hypothesis. We undertook the characterization of the capillary bed of the rat frontal cortex and their permeability properties in short-term and long-term diabetic rats. Methods. Diabetes was induced by strepozotocin injection. Rats were maintained hyperglycaemic without insulin treatment during 4 to 5 months (short-term) and 8 to 13 months (long-term). Rats from an additional short-term hyperglycaemic group received an injection of exogenous dinitrophenylated albumin 15 min before being killed. Tissues were processed for electron microscopy and quantitative immunocytochemistry. Endogenous and dinitrophenylated exogenous albumin were revealed with high resolution over the capillary wall using specific antibodies and the protein A-gold complex. Morphometrical analyses were carried out. Results. Albumin is transported across endothelial cells by plasmalemmal vesicles or caveolae and larger vacuolar structures. This transport increased in diabetic rats by an increment in the number of vesicles. Albumin distribution across the capillary basement membrane showed that the restrictive properties of the basement membrane present in normoglycaemic rats are altered in the diabetic condition, as was its thickness. Similar alterations of the basement membrane structure and function were encountered in old normoglycaemic rats but to a lesser extent. Conclusion/interpretation. The results indicate that diabetes seems to accelerate the ageing process of the vascular wall and that the central nervous system capillary bed is also a target for diabetic microangiopathy.

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“…ncreased synthesis of basement membrane components, fibronectin, collagen IV, and laminin is closely associated with vascular basement membrane thickening, a histological hallmark of diabetic retinopathy (1)(2)(3)(4)(5). In vivo and in vitro studies have shown that diabetes selectively increases basement membrane gene expression in retinal vascular cells and that the excess synthesis of basement membrane components contributes, at least in part, to the development of thickened vascular basement membranes (6 -9).…”

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confidence: 99%

Effect of Combined Antisense Oligonucleotides Against High-Glucose–and Diabetes-Induced Overexpression of Extracellular Matrix Components and Increased Vascular Permeability

et al. 2006

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The effect of combined antisense oligonucleotides (ASoligos) against overexpression of extracellular matrix (ECM) components, fibronectin, laminin, and collagen IV and on cell monolayer permeability was examined in rat microvascular endothelial cells (RMECs) grown in high glucose medium and on retinal vascular permeability in diabetic rats. RMECs grown in high glucose for 10 days and transfected with combined AS-oligos showed a significantly reduced fibronectin, laminin, and collagen IV protein level. In parallel studies, high-glucose-induced excess monolayer permeability was also reduced in RMECs transfected with the combined AS-oligos. Similarly, diabetic rats intravitreally injected with the combined AS-oligos and examined after 2 months of diabetes showed significant reduction in retinal fibronectin, laminin, and collagen IV expression. In addition, vascular permeability, as determined from extravasation of fluorescein isothiocyanate-BSA in the surrounding areas of the retinal capillaries, was partially reduced in the combined AS-oligos-treated diabetic retinas. Our results indicate that the combined AS-oligos strategy is effective in simultaneously reducing fibronectin, collagen IV, and laminin overexpression and reducing vascular leakage in the retinal capillaries of diabetic rat retinas. The findings suggest that abnormal synthesis of ECM components may contribute to vascular leakage in the diabetic retina. Diabetes 55: 86 -92, 2006

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Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments.

Cited by 70 publications

References 36 publications

Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Morpho-functional studies of the blood-brain barrier in streptozotocin-induced diabetic rats

Effect of Combined Antisense Oligonucleotides Against High-Glucose–and Diabetes-Induced Overexpression of Extracellular Matrix Components and Increased Vascular Permeability

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