Progression of Diabetic Macular Edema: Correlation with Blood–Retinal Barrier Permeability, Retinal Thickness, and Retinal Vessel Diameter

Sander, Birgit; Thornit, Dorte Nellemann; Colmorn, Lotte Berdiin; Strøm, Charlotte; Girach, Aniz; Hubbard, Larry D.; Lund‐Andersen, Henrik; Larsen, Michael

doi:10.1167/iovs.06-1102

Cited by 40 publications

(32 citation statements)

References 11 publications

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“…The breakdown of the BRB is an early sign of vascular damage. Several methods have been applied to evaluate the function of BRB among RCTs and animal studies, including vitreous fluorophotometry [27], PVPR [25], vascular fragility [28], skin capillary resistance [19,23] and the penetration ratio [21]. Albumin leakage [29] indicates the successful treatment of capillary fragility in DR patients.…”

Section: Discussionmentioning

confidence: 99%

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Zhang

Liu

et al. 2014

Sci. China Life Sci.

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Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy (DR). This systematic review critically evaluated the evidence that links calcium dobesilate to DR.In this fixed-effects meta-analysis, a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified. Systematic searches of PUBMED, Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords "diabetic retinopathy" and "calcium dobesilate". The extracted information included the study design, inclusion and exclusion criteria, setting, sample size, participant mean age, treatment regime, mean change in best corrected visual acuity, laboratory parameters, capillary fragility, intraocular pressure and fundus manifestations based on the findings of fluorescent angiography.

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Section: Discussionmentioning

confidence: 99%

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Zhang

Liu

et al. 2014

Sci. China Life Sci.

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“…Extravasation or leakage of serum albumin and other materials out of retinal blood vessels has been described as a marker of retinalblood-vessel damage in humans with retinopathy (Vinores et al, 1990;Vinores et al, 1993b) and has been reported in several rodent models of breakdown of the retina-blood barrier (Vinores et al, 1999;Liu et al, 2004;Tomasek et al, 2006). The breakdown of retinal-blood-barrier function has been shown to involve changes in permeability of retinal endothelial cells (Tomasek et al, 2006), and is associated with edema and thickening of retinal tissues (Gardner et al, 2002;Sander et al, 2007). Our previous studies have shown that the loss of retinal endothelial Tbdn expression is associated with retinal fibrovascular growth and thickening, and occurs in a range of retinopathies (Gendron et al, 2001;Paradis et al, 2002;Wall et al, 2004;Gendron et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Tubedown associates with cortactin and controls permeability of retinal endothelial cells to albumin

Paradis

Islam

Tucker

et al. 2008

Journal of Cell Science

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Tubedown (Narg1, Tbdn), a member of the Nat1 family of proteins, associates with the acetyltransferase Ard1 and exerts an angiostatic function in adult retinal-blood-vessel homeostasis. The purpose of the present study was to gain a better understanding of the nature of the Tbdn protein complex and how it might exert a homeostatic influence on blood vessels. Immunoprecipitation of Tbdn from endothelial cells followed by gel electrophoresis and liquid-chromatography–tandem-mass-spectrometry identified the actin-cytoskeleton-binding protein cortactin as a co-immunopurifying species. Western blotting confirmed the association between Tbdn and cortactin. Immunofluorescence confocal microscopy revealed that Tbdn colocalizes with cortactin and F-actin in cytoplasmic regions and at the cortex of cultured endothelial cells. Because cortactin is known to regulate cellular permeability through its interaction with the actin cytoskeleton, a process that is crucial for endothelial cell homeostasis, the role of Tbdn on endothelial cell permeability was examined. Knockdown of Tbdn expression in endothelial cells led to the co-suppression of Ard1 protein expression and to a significant increase in cellular permeability measured by the transit of FITC-albumin across the cellular monolayer. Furthermore, the proliferative retinal neovascularization and thickening resulting from induction of Tbdn knockdown in endothelium in transgenic mice was associated with a significant increase in extravasation or leakage of albumin from abnormal retinal blood vessels in vivo. These results provide evidence that an association occurs between Tbdn and cortactin, and that Tbdn is involved in the regulation of retinal-endothelial-cell permeability to albumin. This work implicates a functional role for Tbdn in blood-vessel permeability dynamics that are crucial for vascular homeostasis.

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“…Visual loss primarily occurs due to increased permeability of retinal vessels (diabetic macular edema) [3] and retinal neovascularization (proliferative diabetic retinopathy) [4,5]. As DR pathogenesis is multifactorial [6][7][8], precise molecular mechanisms therein are still not well understood.…”

Section: Introductionmentioning

confidence: 99%

Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR). In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. Methods: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs. The relationship between O-GlcNAcylation and STAT3 was further delineated by immunoprecipitation and Western blot analysis. Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot. Results: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions. In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose. While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes. Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously. Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway. Conclusion: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.

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Progression of Diabetic Macular Edema: Correlation with Blood–Retinal Barrier Permeability, Retinal Thickness, and Retinal Vessel Diameter

Cited by 40 publications

References 11 publications

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Tubedown associates with cortactin and controls permeability of retinal endothelial cells to albumin

Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells

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