Adhesion molecules (ICAM-1 and VCAM-1) and diabetic retinopathy in type 2 diabetes

Khalfaoui, Taoufik; Lizard, Gérard; Ouertani-Meddeb, A.

doi:10.1007/s10735-007-9159-5

Cited by 61 publications

(55 citation statements)

References 27 publications

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“…They play a main role in the cellular adhesion mechanisms characterized by cell-to-cell and cell-to-extracellular matrix (ECM) interactions for biological signal transducers in these interactions [40,41].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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Section: Discussionmentioning

confidence: 99%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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“…The pathogenesis of diabetic retinopathy has lately been recognized to involve low-grade, chronic inflammation[1], [2], [3], proposed to be the result of persistent hyperglycemia as well as of dyslipidemia[1], [4], [5]. Up-regulation of inflammatory mediators and adhesion molecules are early features of diabetic retinopathy[6], leading to accumulation of leukocytes, altered vessel reactivity and subsequent activation of receptors and transcription factors, ultimately resulting in apoptosis or proliferation of various cell types in the retina[5], [7], e.g., loss of pericytes and proliferation of endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…Up-regulation of inflammatory mediators and adhesion molecules are early features of diabetic retinopathy[6], leading to accumulation of leukocytes, altered vessel reactivity and subsequent activation of receptors and transcription factors, ultimately resulting in apoptosis or proliferation of various cell types in the retina[5], [7], e.g., loss of pericytes and proliferation of endothelial cells. However, it is still a matter of debate whether the inflammatory response is a local phenomenon or not, since clinical studies show variable associations between markers of systemic inflammation and risk of diabetic retinopathy[8], [9], [10].…”

Section: Introductionmentioning

confidence: 99%

Vascular Cellular Adhesion Molecule-1 (VCAM-1) Expression in Mice Retinal Vessels Is Affected by Both Hyperglycemia and Hyperlipidemia

et al. 2010

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BackgroundInflammation has been proposed to be important in the pathogenesis of diabetic retinopathy. An early feature of inflammation is the release of cytokines leading to increased expression of endothelial activation markers such as vascular cellular adhesion molecule-1 (VCAM-1). Here we investigated the impact of diabetes and dyslipidemia on VCAM-1 expression in mouse retinal vessels, as well as the potential role of tumor necrosis factor-α (TNFα).Methodology/Principal FindingsExpression of VCAM-1 was examined by confocal immunofluorescence microscopy in vessels of wild type (wt), hyperlipidemic (ApoE−/−) and TNFα deficient (TNFα−/−, ApoE−/−/TNFα−/−) mice. Eight weeks of streptozotocin-induced diabetes resulted in increased VCAM-1 in wt mice, predominantly in small vessels (<10 µm). Diabetic wt mice had higher total retinal TNFα, IL-6 and IL-1β mRNA than controls; as well as higher soluble VCAM-1 (sVCAM-1) in plasma. Lack of TNFα increased higher basal VCAM-1 protein and sVCAM-1, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. Basal VCAM-1 expression was higher in ApoE−/− than in wt mice and both VCAM-1 mRNA and protein levels were further increased by high fat diet. These changes correlated to plasma cholesterol, LDL- and HDL-cholesterol, but not to triglycerides levels. Diabetes, despite further increasing plasma cholesterol in ApoE−/− mice, had no effects on VCAM-1 protein expression or on sVCAM-1. However, it increased ICAM-1 mRNA expression in retinal vessels, which correlated to plasma triglycerides.Conclusions/SignificanceHyperglycemia triggers an inflammatory response in the retina of normolipidemic mice and up-regulation of VCAM-1 in retinal vessels. Hypercholesterolemia effectively promotes VCAM-1 expression without evident stimulation of inflammation. Diabetes-induced endothelial activation in ApoE−/− mice seems driven by elevated plasma triglycerides but not by cholesterol. Results also suggest a complex role for TNFα in the regulation of VCAM-1 expression, being protective under basal conditions but pro-inflammatory in response to diabetes.

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“…3,4 Increased ICAM-1, vascular cell adhesion molecule-1, and e-selectin levels were found in the serum from patients with diabetic microangiopathy. [5][6][7] In diabetic animal models, increased retinal ICAM-1 expression is believed to be responsible for leukocyte adhesion or leukostasis and increased vascular permeability. Leukostasis is believed to contribute to capillary nonperfusion and local ischemia, which subsequently induces the overexpression of vascular endothelial growth factor (VEGF).…”

mentioning

confidence: 99%

Activation of the Wnt Pathway Plays a Pathogenic Role in Diabetic Retinopathy in Humans and Animal Models

Chen

Zhou

et al. 2009

The American Journal of Pathology

134

189

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Although Wnt signaling is known to mediate multiple biological and pathological processes, its association with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of ␤-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of lowdensity lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts , were also elevated in the DR models. The high glucose-induced activation of ␤-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target. Diabetic retinopathy (DR), the leading cause of blindness in the working age population, represents a common concern in types 1 and 2 of diabetes mellitus (DM). 1 Accumulating evidence suggests that DR is a chronic inflammatory disorder.2 Retinal inflammation is believed to play a causative role in vascular leakage, which can lead to diabetic macular edema, and in retinal neovascularization (NV). It has been shown that levels of soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 are significantly higher in the vitreous from patients with proliferative diabetic retinopathy than in nondiabetic vitreous. 3,4 Increased ICAM-1, vascular cell adhesion molecule-1, and e-selectin levels were found in the serum from patients with diabetic microangiopathy. [5][6][7] In diabetic animal models, increased retinal ICAM-1 expression is believed to be responsible for leukocyte adhesion or leukostasis and increased vascular permeability. Leukostasis is believed to contribute to capillary nonperfusion and local ischemia, which subsequently induces the overexpression of vascular endothelial growth factor (VEGF). 8 -11 Increased VEGF levels are responsible for the retinal vascular leakage and retinal NV.12,13 Recent studies have indicated that oxidative stress, induced by hyperglycemia, contributes to retinal inflammation in diabetes.14,15 However, the pathogenic mechanisms by which diabetes and oxidative stress induce inflammation are not certain at the present time.Wnts are a group of secreted, cysteine-rich glycoproteins, which bind to a coreceptor complex of frizzled (Fz) receptors and low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6) and regulate expression of a number of target genes through an intracellular signaling pathway, namely the Wnt pathway. 16 In the absence of Wnt ligands, ␤-catenin, a down-stream effector of the canonical Wnt pathway, is phosphorylated by a pro...

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Adhesion molecules (ICAM-1 and VCAM-1) and diabetic retinopathy in type 2 diabetes

Cited by 61 publications

References 27 publications

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Vascular Cellular Adhesion Molecule-1 (VCAM-1) Expression in Mice Retinal Vessels Is Affected by Both Hyperglycemia and Hyperlipidemia

Activation of the Wnt Pathway Plays a Pathogenic Role in Diabetic Retinopathy in Humans and Animal Models

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