Increased H2O2, vascular endothelial growth factor and receptors in the retina of the BBZ/WOR diabetic rat

Ellis, E. Ann; Guberski, Dennis L.; Somogyi-Mann, Marta; Grant, Maria B.

doi:10.1016/s0891-5849(99)00216-6

Cited by 141 publications

(97 citation statements)

References 38 publications

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“…14 Prolonged hyperglycemia induces increased levels of ROS such as hydrogen peroxide, hydroxyl radicals and super oxide anions. 19,20 Hyperglycemia and ROS have also been correlated with an elevation of MMP-9 expression and activity that can be attenuated by treatment with antioxidants. 17 It is apparent that in the development of diabetes proteinase expression may be increased by a variety of biochemical mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

Giebel

Menicucci

McGuire

et al. 2005

Laboratory Investigation

276

232

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One of the early features of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. The aim of this study was to examine the expression of extracellular proteinases in an animal model of early diabetic retinopathy and to determine their role in the alteration of the BRB. Matrix metalloproteinase (MMP) expression was studied in the retinas of rats with 12 weeks of diabetes. The role of MMPs in regulating tight junction function was investigated in retinal endothelial and pigment epithelial cells by measuring transepithelial electrical resistance (TER). The retinas of diabetic animals demonstrated elevated levels of MMP-2, MMP-9 and MMP-14 messenger RNA. A significant increase in the production of MMP-9 was seen when cells were exposed to high glucose conditions. Both cell types treated with purified MMP-2 or MMP-9 were found to have alterations of tight junction function as shown by decreased TER. Western blot analysis of cell extracts treated with MMP-2 or MMP-9, revealed specific degradation of the tight junction protein, occludin. Results suggest that elevated expression of MMPs in the retina may facilitate an increase in vascular permeability by a mechanism involving proteolytic degradation of the tight junction protein occludin followed by disruption of the overall tight junction complex.

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Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

Giebel

Menicucci

McGuire

et al. 2005

Laboratory Investigation

276

232

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show abstract

“…in the absence of neovascularisation [30][31][32][33][34][35]. Interestingly, other formulations of α-lipoic acid, given for shorter periods, produced complete inhibition of VEGF in the diabetic retina [10].…”

Section: Discussionmentioning

confidence: 99%

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

et al. 2006

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Aims/hypothesis: Hyperglycaemia-induced mitochondrial overproduction of reactive oxygen species (ROS) is central to the pathogenesis of endothelial damage in diabetes. R-(+)-α-lipoic acid has advantages over classic antioxidants, as it distributes to the mitochondria, is regenerated by glycolytic flux, and has a low redox potential. Methods: To assess the effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: nondiabetic controls, untreated diabetic controls, and diabetic rats treated with 60 mg/kg bodyweight R-(+)-α-lipoic acid i.p. for 30 weeks. Quantitative retinal morphometry included acellular occluded capillaries and pericyte numbers. The effects of R-(+)-α-lipoic acid on parameters of oxidative and nitrative stress, AGE and its receptor and nuclear factor kappa B (NFκB) were assessed by immunoblotting, and NFκB activation by electrophoretic mobility shift assay. Angiopoietin-2 and vascular endothelial growth factors were also determined by immunoblotting. Results: After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1±10.6 acellular capillary segments [ac]/mm 2 of retinal area) compared with nondiabetic (19.8±5

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“…The BBZDR/Wor rat was produced using the BBZDP/Wor (BB rat with an Iddm2 type 1 genetic locus) and mating with lean BBZ/Wor rats (BB rat with Zucker diabetic gene) to remove the Iddm2 locus. The obese male BBZDR/Wor rat spontaneously develops type 2 diabetes at 10 weeks of age (100%) when fed standard rat chow (18,19). The obese BBZDR/Wor rat is lymphopenic, hyperinsulinemic with peripheral insulin resistance and develops spontaneous autoimmune non-insulin-dependent diabetes mellitus at an age of 70 days (18).…”

Section: Methodsmentioning

confidence: 99%

Pioglitazone Normalizes Insulin Signaling in the Diabetic Rat Retina through Reduction in Tumor Necrosis Factor α and Suppressor of Cytokine Signaling 3

Jiang

Thakur

Bheemreddy

et al. 2014

Journal of Biological Chemistry

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Increased H2O2, vascular endothelial growth factor and receptors in the retina of the BBZ/WOR diabetic rat

Cited by 141 publications

References 38 publications

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

Pioglitazone Normalizes Insulin Signaling in the Diabetic Rat Retina through Reduction in Tumor Necrosis Factor α and Suppressor of Cytokine Signaling 3

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