Methylglyoxal induces hyperpermeability of the blood–retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases

Kim, Jung-Hyun; Kim, Chan-Sik; Lee, Yun Mi; Jo, Kyuhyung; Shin, So Dam; Kim, Jin Sook

doi:10.1007/s00417-011-1912-5

Cited by 35 publications

(19 citation statements)

References 40 publications

(45 reference statements)

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“…In our previous study, MGO disrupts the tight junction protein, leading to breakage of the BRB [24]. EP was tested for its ability to inhibit BRB breakage in retinas.…”

Section: Resultsmentioning

confidence: 99%

Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

Kim

Lee²,

Kim³

et al. 2013

Journal of Diabetes Research

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Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP) on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB) breakage, we have used intravitreally methylglyoxal-(MGO-) injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.

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“…In our previous study, MGO disrupts the tight junction protein, leading to breakage of the BRB [24]. EP was tested for its ability to inhibit BRB breakage in retinas.…”

Section: Resultsmentioning

confidence: 99%

Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

Kim

Lee²,

Kim³

et al. 2013

Journal of Diabetes Research

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“…Endothelial cells of retinal vessels normally have tight junctions that maintain the inner blood-retinal barrier (BRB). 30 During RNV, new retinal vessels are deficient in endothelial tight junctions, leading to retinal vascular hyperpermeability and inflammation that disrupt normal retinal tissue or function. 31 In the BRB, the main physical barrier is formed by retinal endothelial cells, which have a key role in the expression of S100A4 during RNV.…”

Section: Discussionmentioning

confidence: 99%

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Cheng

Xing

2016

Eye

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Background To investigate the underlying mechanism of S100A4 function and whether it has a role in retinal neovascularization (RNV) in a mouse model of oxygen-induced retinopathy (OIR). Methods Retinas from a mouse model of OIR were treated with and without an intravitreous injection of adenoviral-S100A4-RNAi or adenoviral green fluorescence protein (GFP) at postnatal day 12 (P12). At P17, the efficacy of adenoviral gene transfer was assessed using fluorescence microscopy and western blot analysis. RNV was evaluated by wholemount immunofluorescence staining of the mouse retina and by counting the number of pre-retinal neovascular cells. Protein and mRNA expression levels of S100A4, brainderived growth factor (BDNF), and vascular endothelial growth factor (VEGF) were measured using western blot analysis and real-time PCR. Results Retinal S100A4 levels were positively correlated with the progression of RNV. In the OIR-S100A4-RNAi group, both protein and mRNA expression levels of S100A4 in the retina significantly decreased at P17 compared with those in the OIR group. Ad-S100A4-RNAi transfer was clearly demonstrated by GFP fluorescence in many layers of the retina 5 days after the Ad-S100A4-RNAi transfer. Whole-mount immunofluorescence staining of the retina and quantification of the pre-retinal neovascular cells demonstrated that RNV was significantly inhibited. Meanwhile, the levels of the transcription and translation of BDNF,

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“…This ultimately leads to fibrosis and retinal detachment. Endothelial cells of the normal retinal vessels have tight junctions that maintain normal inner blood–retinal barrier (BRB)function [12]. During RNV, the new retinal vessels become deficient in such endothelial tight junctions leading to retinal vascular hyperpermeability and inflammation that disrupt normal retinal tissue/function [13].…”

Section: Retinal Neovascularizationmentioning

confidence: 99%

“…In the BRB, the main physical barrier is formed by retinal endothelial cells, but pericytes and retinal glia were found to contribute to the maintenance of the BRB as well [14–16]. Therefore, In addition to the loss of endothelial cell tight junction, loss of retinal pericytes during DR abrogates structural vascular integrity and contributes to retinal vascular leakage [12,17]. …”

Section: Retinal Neovascularizationmentioning

confidence: 99%

Targeting neovascularization in ischemic retinopathy: recent advances

Al‐Shabrawey

El‐Sherbiny

Nussbaum

et al. 2013

Expert Review of Ophthalmology

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Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities.

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Methylglyoxal induces hyperpermeability of the blood–retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases

Cited by 35 publications

References 40 publications

Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

Silencing of S100A4, a metastasis-associated protein, inhibits retinal neovascularization via the downregulation of BDNF in oxygen-induced ischaemic retinopathy

Targeting neovascularization in ischemic retinopathy: recent advances

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