Increased lipid peroxide levels and myeloperoxidase activity in the vitreous of patients suffering from proliferative diabetic retinopathy

Augustin, Albert J.; Breipohl, W.; Böker, Thorsten; Lutz, Joachim; Spitznas, Manfred

doi:10.1007/bf00921959

Cited by 61 publications

(32 citation statements)

References 33 publications

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“…Patients with diabetic retinopathy have elevated blood levels of thio-barbituric acid reacting substances (a measure of oxidative stress and lipid peroxidation, and those in type I are higher than those in type II [6,7]. We have recently demonstrated that oxidative and inflammatory reactions are detectable in the vitreous body of eyes suffering from PDR and PVR with a higher inflammatory activity in diabetic eyes [8,9]. Tumor necrosis factor α (TNF-α), a cytokine also released during ischemia, which exerts changes of the bloodretina barrier, could be an important mediator of the disease process.…”

Section: Introductionmentioning

confidence: 96%

“…In previous studies we demonstrated elevated levels of lipid peroxides as thiobarbituric acid reacting substances and myeloperoxidase activity in the vitreous and epiretinal membranes from patients with PDR or PVR [8,9,25]. Activation of leukocytes leads to enhanced synthesis of cyclooxygenase and lipoxygenase which convert arachidonic acid into peroxide metabolites that further stimulate cytokine secretion through a positive feedback mechanism [26,27].…”

Section: Tumor Necrosis Factor-αmentioning

confidence: 99%

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Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

et al. 1998

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Purpose: To evaluate epiretinal membranes in proliferative eye disease for the presence of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: Membranes were surgically removed from 66 patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular pucker (MP). Cytokine concentrations were determined by ELISA (VEGF) and bioassay (TNF-α). Results: VEGF was detected in all 66 membranes investigated. The highest VEGF values were found in patients with type I diabetes (mean = 5,994 pg/mg protein). In patients with type II diabetes, the values were at a mean of 1,242 pg/mg protein. When coagulation therapy was performed for longer than 3 months prior to surgery, VEGF was significantly (p < 0.05) reduced. Intermediate levels of VEGF were found in PVR membranes (mean = 1,417 pg/mg protein). The lowest activity was found in MP (mean = 216 pg/mg protein). In contrast, TNF-α was present in 16 PDR membranes, 9 PVR membranes and 8 MP membranes. Conclusion: The presence of VEGF in all membranes investigated indicates that this cytokine plays an important role in angiogenesis in ischemic retinal disease and in membrane growth in proliferative disorders.

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Section: Introductionmentioning

confidence: 96%

Section: Tumor Necrosis Factor-αmentioning

confidence: 99%

Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

et al. 1998

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“…Ischemic diabetic retinal vascular occlusion, resulting from activated granulocytes and monocytes (24), is reversible and reperfusion has been documented angiographically in diabetic eyes (25). Elevated levels of ROI reaction products have been directly correlated with neovascularization in human (26) and rat (27) diabetic eyes, and in eyes with retinopathy of prematurity (28). Both ocular pathologies are strongly correlated with increased VEGF gene expression (8,9,(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.

Kuroki¹,

Voest²,

Amano³

et al. 1996

J. Clin. Invest.

386

243

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Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROIassociated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability. ( J. Clin. Invest. 1996 . 98:1667 -1675 ).

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“…Increased serum lipid peroxides suggesting increased free radical activity is associated with retinopathy and this may have pathogenetic implications [14]. Increased lipid peroxide levels have also been observed in the vitreous of patients suffering from proliferative diabetic retinopathy [15]. Patients with diabetic nephropathy and retinopathy, but not neuropathy, have been found to have elevated plasma TBARS levels but no statistically significant difference was observed when compared with diabetic patients without microangiopathy.…”

Section: Discussionmentioning

confidence: 88%

Elevated lipid peroxides induced angiogenesis in proliferative diabetic retinopathy

Saxena

Srivastava²,

Khanna

2010

j ocul biol dis inform

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Oxidative stress is associated with causation of diabetic vascular complications. A case-control study was undertaken to evaluate the association of platelet thiobarbituric acid reacting substances (TBARS) with the severity of diabetic retinopathy for the first time. Platelet TBARS levels were estimated using standard protocol. Platelet TBARS levels in the cases with non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, and healthy controls were 0.56±0.09, 0.69±0.11 and 0.41±0.1 nmol/h/ 10 8 platelets, respectively. A significant increase in platelet TBARS levels was observed in the cases as compared to controls (p<0.001). Elevated TBARS levels were observed to significantly increase further during the proliferative stage of the disease (p<0.01). The increase in platelet TBARS levels, and thereby at retinal level, is associated with angiogenesis in diabetic retinopathy. Supplemental anti-oxidant therapy in diabetic retinopathy may prevent ocular angiogenesis resulting as a consequence of oxidative stress.

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Increased lipid peroxide levels and myeloperoxidase activity in the vitreous of patients suffering from proliferative diabetic retinopathy

Cited by 61 publications

References 33 publications

Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker

Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.

Elevated lipid peroxides induced angiogenesis in proliferative diabetic retinopathy

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