The Experts below are selected from a list of 2214 Experts worldwide ranked by ideXlab platform
Sayon Roy - One of the best experts on this subject based on the ideXlab platform.
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retinal capillary basement membrane thickening role in the pathogenesis of Diabetic retinopathy
Progress in Retinal and Eye Research, 2021Co-Authors: Sayon Roy, Dongjoon KimAbstract:Vascular basement membrane (BM) thickening has been hailed over half a century as the most prominent histological lesion in Diabetic Microangiopathy, and represents an early ultrastructural change in Diabetic retinopathy (DR). Although vascular complications of DR have been clinically well established, specific cellular and molecular mechanisms underlying dysfunction of small vessels are not well understood. In DR, small vessels develop insidiously as BM thickening occurs. Studies examining high resolution imaging data have established BM thickening as one of the foremost structural abnormalities of retinal capillaries. This fundamental structural change develops, at least in part, from excess accumulation of BM components. Although BM thickening is closely associated with the development of DR, its contributory role in the pathogenesis of DR is coming to light recently. DR develops over several years before clinical manifestations appear, and it is during this clinically silent period that hyperglycemia induces excess synthesis of BM components, contributes to vascular BM thickening, and promotes structural and functional lesions including cell death and vascular leakage in the Diabetic retina. Studies using animal models show promising results in preventing BM thickening with subsequent beneficial effects. Several gene regulatory approaches are being developed to prevent excess synthesis of vascular BM components in an effort to reduce BM thickening. This review highlights current understanding of capillary BM thickening development, role of BM thickening in retinal vascular lesions, and strategies for preventing vascular BM thickening as a potential therapeutic strategy in alleviating characteristic lesions associated with DR.
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Rapid Publication Increased Expression of Basement Membrane Collagen in Human Diabetic Retinopathy
2016Co-Authors: Sayon Roy, Michele Maiello, Mara LorenziAbstract:Basement membrane thickening is the most prominent and characteristic feature of early Diabetic Microangiopathy. Un-known is not only the causative process but also whether the thickening reflects increased synthesis of specific components. Because collagen type IV is uniquely present in basement mem-branes and represents their predominant structural element, we studied its expression in retinas obtained postmortem from five patients with 8±3 yr of diabetes and six nonDiabetic controls. The collagen IV transcript proved to be rare in adult human retina and undetectable by Northern analysis. We thus identi-fied a set of primers and conditions to detect the transcript by the reverse transcriptase polymerase chain reaction and to measure its level relative to an endogenous internal standard (ft-actin mRNA). In the Diabetic patients the levels of collagen IV mRNA were increased twofold over levels in controls, whereas the actin mRNA levels were similar in the two groups. Hence, the collagen IV/actin ratio was 0.53±0.15 in Diabetic samples and 0.24±0.09 in control samples (P = 0.004). These results indicate that diabetes induces a twofold increase in the expression of collagen IV by the cells that synthesize basement membranes in the adult retina (vascular cells). Insofar as high ambient glucose in vitro elicits the same effect, it may be pro-posed that basement membrane thickening in diabetes results from enhanced synthesis of specialized component molecules sustained by hyperglycemia. (J. Clin. Invest. 1994. 93:438-442). Key words: basement membrane thickening * Diabetic Microangiopathy * type IV collagen * polymerase chain reactio
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tight glycemic control regulates fibronectin expression and basement membrane thickening in retinal and glomerular capillaries of Diabetic rats
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Saira Cherian, Sayon Roy, Andre PinheiroAbstract:PURPOSE. To determine whether tight glycemic control prevents development of basement membrane (BM) thickening in retinal and glomerular capillaries of Diabetic rats and whether the extent to which BM thickening develops is linked to fibronectin (FN) overexpression and the degree of hyperglycemia. METHODS. Retinal and renal cortical tissues obtained from the tightly controlled Diabetic (TC), poorly controlled Diabetic (D), and nonDiabetic (N) control rats were subjected to morphometric and biochemical analyses. In both tissues, capillary BM thickening was determined by electron microscopy, and FN protein level was assessed by Western blot analysis. Routine measurements of blood glucose level and glycohemoglobin level were performed throughout the study. RESULTS. The HbA1c level was significantly increased in D rats, but not in TC rats, compared with those of the N rats with a concomitant increase in capillary BM thickness and FN protein expression in retinal and renal tissues. A strong correlation was observed between retinal and glomerular capillary BM thickness (r = 0.79, P = 0.0001), between retinal and kidney FN protein levels (r = 0.7, P = 0.005), between HbAlc and FN protein levels in the retina (r = 0.66, P = 0.006) and kidney (r = .84, P = 0.0003), and between HbAlc level and BM thickness in retinal (r = 0.76, P = 0.0002) and renal tissues (r = 0.64, P = 0.004). CONCLUSIONS. In diabetes BM thickening develops in retinal and glomerular capillaries in a correlated manner. Tight glycemic control may be beneficial in preventing the pathologic development of capillary BM thickening and FN overexpression in retinal and renal tissues, two target tissues of Diabetic Microangiopathy.
Masayoshi Soma - One of the best experts on this subject based on the ideXlab platform.
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complement mediated chronic inflammation is associated with Diabetic microvascular complication
Diabetes-metabolism Research and Reviews, 2013Co-Authors: Takayuki Fujita, Seiichiro Hemmi, Mamiko Kajiwara, Minako Yabuki, Yoshinobu Fuke, Atsushi Satomura, Masayoshi SomaAbstract:BACKGROUND: Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation. METHODS: We investigated the association between Diabetic Microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron. RESULTS: Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia. CONCLUSIONS: Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of Diabetic Microangiopathy in addition to the development of macroangiopathy.
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complement mediated chronic inflammation is associated with Diabetic microvascular complication
Diabetes-metabolism Research and Reviews, 2013Co-Authors: Takayuki Fujita, Seiichiro Hemmi, Mamiko Kajiwara, Minako Yabuki, Yoshinobu Fuke, Atsushi Satomura, Masayoshi SomaAbstract:Background Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation. Methods We investigated the association between Diabetic Microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron. Results Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia. Conclusions Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of Diabetic Microangiopathy in addition to the development of macroangiopathy. Copyright © 2012 John Wiley & Sons, Ltd.
Dongjoon Kim - One of the best experts on this subject based on the ideXlab platform.
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retinal capillary basement membrane thickening role in the pathogenesis of Diabetic retinopathy
Progress in Retinal and Eye Research, 2021Co-Authors: Sayon Roy, Dongjoon KimAbstract:Vascular basement membrane (BM) thickening has been hailed over half a century as the most prominent histological lesion in Diabetic Microangiopathy, and represents an early ultrastructural change in Diabetic retinopathy (DR). Although vascular complications of DR have been clinically well established, specific cellular and molecular mechanisms underlying dysfunction of small vessels are not well understood. In DR, small vessels develop insidiously as BM thickening occurs. Studies examining high resolution imaging data have established BM thickening as one of the foremost structural abnormalities of retinal capillaries. This fundamental structural change develops, at least in part, from excess accumulation of BM components. Although BM thickening is closely associated with the development of DR, its contributory role in the pathogenesis of DR is coming to light recently. DR develops over several years before clinical manifestations appear, and it is during this clinically silent period that hyperglycemia induces excess synthesis of BM components, contributes to vascular BM thickening, and promotes structural and functional lesions including cell death and vascular leakage in the Diabetic retina. Studies using animal models show promising results in preventing BM thickening with subsequent beneficial effects. Several gene regulatory approaches are being developed to prevent excess synthesis of vascular BM components in an effort to reduce BM thickening. This review highlights current understanding of capillary BM thickening development, role of BM thickening in retinal vascular lesions, and strategies for preventing vascular BM thickening as a potential therapeutic strategy in alleviating characteristic lesions associated with DR.
J. E. Tooke - One of the best experts on this subject based on the ideXlab platform.
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reduced microvascular hyperaemia in subjects at risk of developing type 2 non insulin dependent diabetes mellitus
Diabetologia, 1994Co-Authors: A J Jaap, M S Hammersley, Angela C. Shore, J. E. TookeAbstract:Abnormalities of microvascular function may be important in the pathogenesis of Diabetic Microangiopathy. As such changes are already present at diagnosis in patients with Type 2 (non-insulin-dependent) diabetes mellitus, subjects at risk of developing the disease, who had elevated fasting plasma glucose concentrations below the Diabetic range, were studied. The maximal microvascular hyperaemic response to local heating was determined in the feet of 11 subjects with fasting hyperglycaemia and 11 age- and sex-matched control subjects. There was reduced maximal hyperaemia in the subjects with fasting hyperglycaemia (1.01 [0.71-1.57]V, median and range), when compared to control subjects (1.41 [1.32-2.13]V, p < 0.001). It is unlikely that this limited vasodilation is a result of the mild degree of hyperglycaemia observed in the subjects included in this study. Further studies are therefore required to address the possible mechanisms of limited microvascular reactivity in subjects at risk of developing Type 2 diabetes.
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relation of skin capillary pressure in patients with insulin dependent diabetes mellitus to complications and metabolic control
The New England Journal of Medicine, 1992Co-Authors: D D Sandeman, A C Shore, J. E. TookeAbstract:Abstract Background Microvascular disease is a major problem in patients with diabetes mellitus. It has been suggested that Diabetic Microangiopathy may result from an increase in capillary blood flow and capillary hypertension, but direct evidence of capillary hypertension in such patients is lacking. Methods We measured capillary pressure at the summit of the capillary loop by direct microcannulation of skin nail-fold capillaries and a dynamic method of pressure measurement in 29 patients with insulin-dependent (Type I) diabetes and 29 normal subjects matched for age and sex. Among the Diabetic patients, 7 had had diabetes for less than one year, 12 had incipient nephropathy (albumin excretion, 20 to 200 μ per minute), and 10 had overt nephropathy (albumin excretion, >200 μg per minute). In addition, seven patients with no evidence of nephropathy were studied before and after three months of improved glycemic control. Results The median capillary pressure in the Diabetic patients was 20.4 mm Hg (range, ...
Takayuki Fujita - One of the best experts on this subject based on the ideXlab platform.
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complement mediated chronic inflammation is associated with Diabetic microvascular complication
Diabetes-metabolism Research and Reviews, 2013Co-Authors: Takayuki Fujita, Seiichiro Hemmi, Mamiko Kajiwara, Minako Yabuki, Yoshinobu Fuke, Atsushi Satomura, Masayoshi SomaAbstract:BACKGROUND: Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation. METHODS: We investigated the association between Diabetic Microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron. RESULTS: Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia. CONCLUSIONS: Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of Diabetic Microangiopathy in addition to the development of macroangiopathy.
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complement mediated chronic inflammation is associated with Diabetic microvascular complication
Diabetes-metabolism Research and Reviews, 2013Co-Authors: Takayuki Fujita, Seiichiro Hemmi, Mamiko Kajiwara, Minako Yabuki, Yoshinobu Fuke, Atsushi Satomura, Masayoshi SomaAbstract:Background Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation. Methods We investigated the association between Diabetic Microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron. Results Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia. Conclusions Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of Diabetic Microangiopathy in addition to the development of macroangiopathy. Copyright © 2012 John Wiley & Sons, Ltd.