Advanced Glycation End Products Increase Retinal Vascular Endothelial Growth Factor Expression.

Lu, Mei-Hua; Kuroki, Masahide; Amano, Shoichi; Tolentino, Michael J.; Keough, Karen; Kim, Ivana K.; Bucala, Richard; Adamis, Anthony P.

doi:10.1097/00006982-199805000-00030

Cited by 100 publications

(130 citation statements)

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“…These include not only glucose [37] but also advanced glycation end products (AGEs) [38] and protein kinase-C activation [39,40]. Of particular relevance to our study, angiotensin II also stimulates VEGF expression, an action mediated by the AT1 receptor as indicated by the attenuation of this effect by the AT1 receptor antagonist, losartan [13,41].…”

Section: Discussionmentioning

confidence: 85%

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

et al. 2000

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Despite laser photocoagulation therapy, diabetic retinopathy remains a common cause of visual impairment and blindness [1], principally as a consequence of proliferative retinopathy and macular oedema. Although the pathogenesis of these retinal disorders characterized by retinal neovascularization and exudation is incompletely understood, recent evidence has implicated the vascular endothelial growth factor (VEGF), a permeability-inducing and endothelial cell selective angiogenic glycoprotein as a key factor [2±4].Although plasma renin is suppressed in diabetes, experimental evidence suggests that the tissue reninangiotensin system (RAS) is activated in the setting of chronic hyperglycaemia [5] and that its blockade underlies the beneficial effects of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy [6] and cardiovascular disease [7]. Previous

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Section: Discussionmentioning

confidence: 85%

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

et al. 2000

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“…In addition, glucose degradation products and advanced glycation end products are known to induce VEGF expression in vitro, although the in vivo relevance of these pathways remains to be demonstrated. Laser burns destroy the ischemic retinal tissue that is a source of intraocular VEGF (25,26), which is followed by alterations in gene expression, as has been observed in mice retina after PRP. Specifically, genes inhibiting VEGF expression (e.g., angiotensin II type 2 receptor) were found to be upregulated, whereas genes promoting VEGF expression (e.g., fibroblast growth factors 14 and 16, interleukin-1␤, calcitonin receptor-like receptor, and plasminogen activator inhibitor 2) were found to be downregulated (27).…”

Section: Research Design Andmentioning

confidence: 83%

Metabolic Control of Diabetes Is Associated With an Improved Response of Diabetic Retinopathy to Panretinal Photocoagulation

Kotoula

Koukoulis²,

Ζιντζαράς³

et al. 2005

Diabetes Care

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OBJECTIVE -To study the influence of glycemic control and the presence of microalbuminuria on the initial response to panretinal photocoagulation (PRP) in patients with a high-risk proliferative diabetic retinopathy (PDR).RESEARCH DESIGN AND METHODS -This was a prospective cohort study with a two-by-two factorial design. We used full-scattered PRP to treat 115 eyes of type 2 diabetic patients who have high-risk PDR. HbA 1c (A1C) and albumin levels in 24-h urine were constantly monitored during the preenrollment, treatment, and posttreatment periods. At a follow-up visit 12 weeks after the last PRP session, the fundus was examined for characteristics of regression from high-risk PDR and the response to PRP was determined to be successful or unsuccessful. The eyes were categorized into four groups based on average A1C levels and the presence or absence of microalbuminuria. The data were analyzed using a logistic regression model. Our statistical analysis determined the probability of achieving a satisfactory response to PRP in association with A1C levels and the presence or absence of microalbuminuria.RESULTS -Of the 115 eyes examined, 65 (56.5%) had a successful initial response to PRP and 50 (43.5%) did not. The probability of a satisfactory response to PRP was related to A1C levels (P Ͻ 0.05) but not to microalbuminuria and its interaction with hemoglobin glycosylation (P Ն 0.05).CONCLUSIONS -Low levels of hemoglobin glycosylation (A1C Ͻ8%) during the pretreatment, treatment, and posttreatment periods are associated with a regression of proliferative diabetic retinopathy after PRP. Diabetes Care 28:2454 -2457, 2005D iabetic retinopathy has been the subject of in-depth study for the last 3 decades, during which time randomized and controlled multicenter clinical trials have provided important information about the natural history and treatment of the disease. Panretinal photocoagulation (PRP) is the treatment of choice for proliferative diabetic retinopathy (PDR) (1). However, some patients do not respond to PRP and eventually experience legal blindness (2).Hyperglycemia is an important risk factor for the development of microvascular disease in diabetic patients. There is a direct relation between the degree of glycemic control and the incidence and progression of retinopathy (3-11). However, the influence of metabolic control of diabetes on the response of diabetic retinopathy to PRP has not been previously studied. Linking PRP effectiveness with metabolic control of diabetes may provide useful information for visual prognosis in diabetic patients.Data from most studies suggest an association between diabetic nephropathy, as manifested by microalbuminuria, and diabetic retinopathy (12). There are no data, however, on whether the presence of microalbuminuria is a negative prognostic factor for the efficacy of PRP. The aim of this study was to assess the influence of the degree of glycemic control and microalbuminuria on the initial response to PRP in patients with high-risk PDR. RESEARCH DESIGN AND METHODS -Thi...

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“…The breakdown of the BRB occurs in patients with diabetic retinopathy [27]. Several studies have suggested that AGEs induce vasopermeability of the retina by increasing VEGF production [14,23,[28][29][30][31] and disrupt the BRB by decreasing tight junction proteins, such as occludin and ZO-1 [32]. However, the role of AGEs in diabetic neuropathy remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood–nerve barrier by stimulating the release of TGF-β and vascular endothelial growth factor (VEGF) by pericytes

et al. 2011

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Aims/hypothesis The breakdown of the blood-nerve barrier (BNB) is considered to be a key step in diabetic neuropathy. Although basement membrane hypertrophy and breakdown of the BNB are characteristic features of diabetic neuropathy, the underlying pathogenesis remains unclear. The purpose of the present study was to identify the possible mechanisms responsible for inducing the hypertrophy of basement membrane and the disruption of the BNB after exposure to AGEs. Methods The newly established human peripheral nerve microvascular endothelial cell (PnMEC) and pericyte cell lines were used to elucidate which cell types constituting the BNB regulate the basement membrane and to investigate the effect of AGEs on the basement membrane of the BNB using western blot analysis. Results Fibronectin, collagen type IV and tissue inhibitor of metalloproteinase (TIMP-1) protein were produced mainly by peripheral nerve pericytes, indicating that the basement membrane of the BNB is regulated mainly by these cells. AGEs reduced the production of claudin-5 in PnMECs by increasing autocrine signalling through vascular endothelial growth factor (VEGF) secreted by the PnMECs themselves.Furthermore, AGEs increased the amount of fibronectin, collagen type IV and TIMP-1 in pericytes through a similar upregulation of autocrine VEGF and transforming growth factor (TGF)-β released by pericytes. Conclusions/interpretation These results indicate that pericytes may be the main regulators of the basement membrane at the BNB. AGEs induce basement membrane hypertrophy and disrupt the BNB by increasing autocrine VEGF and TGF-β signalling by pericytes under diabetic conditions.

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Advanced Glycation End Products Increase Retinal Vascular Endothelial Growth Factor Expression.

Cited by 100 publications

References 0 publications

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

Metabolic Control of Diabetes Is Associated With an Improved Response of Diabetic Retinopathy to Panretinal Photocoagulation

Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood–nerve barrier by stimulating the release of TGF-β and vascular endothelial growth factor (VEGF) by pericytes

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