Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

Dahrouj, Mohammad; Desjardins, Danielle; Liu, Yue-Ying; Crosson, Craig E.

doi:10.1016/j.exer.2015.06.004

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…Specifically, the molecule exerts its inhibitory action by blocking the V domain of RAGE . Although this is a recently described RAGE inhibitor, several in vivo and in vitro studies have validated the binding specificity of FPS‐ZM1 with RAGE and the blocking of RAGE‐mediated downstream signaling cascades . The concentration of FPS‐ZM1 used in our experiments was also well within the effective and nontoxic levels as described in the literature .…”

Section: Discussionsupporting

confidence: 69%

Nonenzymatic glycation interferes with fibronectin‐integrin interactions in vascular smooth muscle cells

et al. 2017

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Objective We aimed to investigate whether advanced non-enzymatic glycation of the extracellular matrix (ECM) protein, fibronectin, impacts its normal integrin-mediated interaction with arteriolar vascular smooth muscle cells (VSMC). Methods Atomic force microscopy (AFM) was performed on cultured VSMC from rat cremaster arterioles to study native and glycated fibronectin (FN and gFN) interactions with cellular integrins. AFM probes were functionalized with FN or gFN or with native or glycated albumin (gAlb) as controls. Results VSMC showed increased adhesion probability to gFN (72.9 ± 3.5 %) compared to native FN (63.0 ± 1.6 %). VSMCs similarly showed increased probability of adhesion (63.8 ± 1.7 %) to gAlb compared to native Alb (40.1 ± 4.7 %). Adhesion of native FN to VSMC was α5 and β1 integrin-dependent whereas adhesion of gFN to VSMC was integrin-independent. The RAGE-selective inhibitor, FPS-ZM1, blocked gFN (and gAlb) adhesion suggesting that adhesion of glycated proteins was RAGE-dependent. Interaction of FN with VSMC was not altered by soluble gFN while soluble native FN did not inhibit adhesion of gFN to VSMC. In contrast, gAlb inhibited adhesion of gFN to VSMC in a concentration-dependent manner. Conclusions Glycation of FN shifts the nature of cellular adhesion from integrin- to RAGE-dependent mechanisms.

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Section: Discussionsupporting

confidence: 69%

Nonenzymatic glycation interferes with fibronectin‐integrin interactions in vascular smooth muscle cells

et al. 2017

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“…Therefore, these multiple factors may be influenced by sVEGFR-2 in DME, suggesting that anti-VEGFR therapy could be considered for macular edema in DME patients. This idea is supported by reports that VEGF-induced breakdown of the retinal pigment epithelium (RPE) barrier was blocked by pretreatment with relatively selective VEGFR-2 antagonists in both ARPE-19 and primary RPE cells [51] , and that the Glyc-alb-induced breakdown of RPE function was blocked by a relatively selective VEGFR-2 antagonist in both animal and tissue culture models [52] . This suggests that both anti-VEGF therapy and anti-VEGFR-2 therapy should be considered for DME.…”

Section: Discussionsupporting

confidence: 66%

Aqueous Humor Levels of Soluble Vascular Endothelial Growth Factor Receptor and Inflammatory Factors in Diabetic Macular Edema

et al. 2017

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Aqueous levels of soluble vascular endothelial growth factor receptor (sVEGFR) and inflammatory factors were measured in 35 patients (37 eyes) with diabetic macular edema (DME)receiving anti-vascular endothelial growth factor (VEGF) therapy. Aqueous levels of growth factors (VEGF, placental growth factor [PlGF], and platelet-derived growth factor AA [PDGF-AA]), sVEGFR-1 and -2, soluble intercellular adhesion molecule 1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, -8, -12, and -13, and interferon-inducible 10-kDa protein (IP-10) were significantly higher in the DME group than in the nondiabetic control group. The sVEGFR-2 level was significantly correlated with the neurosensory retinal thickness, as well as with the levels of growth factors (VEGF and PDGF-AA) and inflammatory factors (MCP-1, IL-6, and IL-8). Three growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other, as were sVEGFR-1 or -2 and the inflammatory factors (MCP-1, IL-6, IL-8, and IP-10). These findings suggest that sVEGFRs and growth/inflammatory factors have an important role in DME.

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“…Similarly to other reports 7 – 12 our previous studies 13 , 14 have demonstrated that in experimentally induced type 1 diabetic (T1D) rats, several cell types of the retina, including astrocytes, Müller glia cells, photoreceptors, retinal pigment epithelium (RPE), amacrine and ganglion cells are already affected, even prior to significant apoptosis or clinically detectable vasculopathy.…”

Section: Introductionsupporting

confidence: 78%

Histological Evaluation of Diabetic Neurodegeneration in the Retina of Zucker Diabetic Fatty (ZDF) Rats

Szabó

Énzsöly

Dékány

et al. 2017

Sci Rep

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In diabetes, retinal dysfunctions exist prior to clinically detectable vasculopathy, however the pathology behind these functional deficits is still not fully established. Previously, our group published a detailed study on the retinal histopathology of type 1 diabetic (T1D) rat model, where specific alterations were detected. Although the majority of human diabetic patients have type 2 diabetes (T2D), similar studies on T2D models are practically absent. To fill this gap, we examined Zucker Diabetic Fatty (ZDF) rats - a model for T2D - by immunohistochemistry at the age of 32 weeks. Glial reactivity was observed in all diabetic specimens, accompanied by an increase in the number of microglia cells. Prominent outer segment degeneration was detectable with changes in cone opsin expression pattern, without a decrease in the number of labelled elements. The immunoreactivity of AII amacrine cells was markedly decreased and changes were detectable in the number and staining of some other amacrine cell subtypes, while most other cells examined did not show any major alterations. Overall, the retinal histology of ZDF rats shows a surprising similarity to T1D rats indicating that despite the different evolution of the disease, the neuroretinal cells affected are the same in both subtypes of diabetes.

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Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

Cited by 23 publications

References 48 publications

Nonenzymatic glycation interferes with fibronectin‐integrin interactions in vascular smooth muscle cells

Nonenzymatic glycation interferes with fibronectin‐integrin interactions in vascular smooth muscle cells

Aqueous Humor Levels of Soluble Vascular Endothelial Growth Factor Receptor and Inflammatory Factors in Diabetic Macular Edema

Histological Evaluation of Diabetic Neurodegeneration in the Retina of Zucker Diabetic Fatty (ZDF) Rats

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