| Methylglyoxal induces hyperpermeability of the blood-retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases. | |
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MedLine Citation:
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PMID: 22249316 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: One of the early signs of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. Methylglyoxal (MGO) is a cytotoxic metabolite that is produced from glycolysis in vivo. Elevated levels of MGO are observed in a number of pathological conditions, including neurodegenerative disorders and diabetic complications. Herein, we hypothesize that increased levels of MGO disrupt the tight junction protein known as occludin protein by matrix metalloproteinases (MMPs), leading to breakage of the BRB. METHODS: MGO was intravitreally injected into eyes of rats. BRB leakage, MMPs activity, and occludin were investigated in intravitreally MGO-injected eyes. RESULTS: When normoglycemic rats were intravitreally injected with 400 μM MGO, there was widespread leakage of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) from the retinal vasculature when compared to control retinas. In addition, MGO-injected retinas demonstrated increases of both activity and expression of MMP-2 and MMP-9, and the degradation of occludin was found in the MGO-injected retinas. CONCLUSIONS: The results suggest that the activation of MMPs by elevated levels of MGO in the retina may facilitate an increase in vascular permeability by a mechanism involving proteolytic degradation of occludin. These findings may have implications for the role of MGO in the pathogenesis of diabetic retinopathy. |
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Authors:
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Junghyun Kim; Chan-Sik Kim; Yun Mi Lee; Kyuhyung Jo; So Dam Shin; Jin Sook Kim |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
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Title: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Volume: - ISSN: 1435-702X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8205248 Medline TA: Graefes Arch Clin Exp Ophthalmol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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