Serum markers of oxidative stress and severity of diabetic retinopathy.

Hartnett, M. Elizabeth; Stratton, Russell J.; Browne, Roy; Rosner, B; Lanham, Richard J.; Armstrong, David T.

doi:10.2337/diacare.23.2.234

Cited by 138 publications

(93 citation statements)

References 7 publications

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“…In diabetic animals, AGE inhibitors such as aminoguanidine can attenuate the formation of retinal microvascular lesion; however, recent studies indicate that this drug can significantly alleviate diabetic retinopathic lesions without affecting the formation of the AGE pentosidine in retinal basement membrane collagen [89]. This effect might be linked with aminoguanidine's antioxidative property rather than AGE inhibitory properties [90] as oxidative imbalances in diabetic retinopathy have also been extensively reported [91,92]. Interestingly, some studies have reported no significant change of retinal vascular lesions after treatment with antioxidants [93].…”

Section: Age Inhibitors and Prevention Of Retinopathymentioning

confidence: 70%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

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Section: Age Inhibitors and Prevention Of Retinopathymentioning

confidence: 70%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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“…27 For instance, immunohistochemical analyses have demonstrated enhanced iNOS expression in the retinas of diabetic patients, 23 and both genetic knockout and pharmacological inhibition of iNOS reduce apoptosis in the inner nuclear layer of the avascular retina in ischemic proliferative retinopathy. 28 In addition, NO may act as an angiogenic mediator by stimulating production of VEGF, which has been strongly implicated in the development of proliferative retinopathy. 29,30 In agreement with these observations, we found that iNOS expression was higher in Akita mouse retinas, and HOG-LDL induced an increase in iNOS expression and NO production in human retinal pericytes.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Nitration of Prostacyclin Synthase Is Associated with Enhanced Retinal Cell Apoptosis in Diabetes

Zou

et al. 2011

The American Journal of Pathology

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The risk of diabetic retinopathy is associated with the presence of both oxidative stress and toxic eicosanoids. Whether oxidative stress actually causes diabetic retinopathy via the generation of toxic eicosanoids, however, remains unknown. The aim of the present study was to determine whether tyrosine nitration of prostacyclin synthase (PGIS) contributes to retinal cell death in vitro and in vivo. Exposure of human retinal pericytes to heavily oxidized and glycated LDL (HOG-LDL), but not native forms of LDL (N-LDL), for 24 hours significantly increased pericyte apoptosis, accompanied by increased tyrosine nitration of PGIS and decreased PGIS activity. Inhibition of the thromboxane receptor or cyclooxygenase-2 dramatically attenuated HOG-LDL-induced apoptosis without restoring PGIS activity. Administration of superoxide dismutase (to scavenge superoxide anions) or L-N G -nitroarginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) restored PGIS activity and attenuated pericyte apoptosis. In Akita mouse retinas, diabetes increased intraretinal levels of oxidized LDL and glycated LDL, induced PGIS nitration, enhanced apoptotic cell death, and impaired blood-retinal barrier function. Chronic administration of tempol, a superoxide scavenger, reduced intraretinal oxidized LDL and glycated LDL levels, PGIS nitration, and retina cell apoptosis, thereby preserving the integrity of blood-retinal barriers. In conclusion, oxidized LDL-mediated PGIS nitration and associated thromboxane receptor stimulation might be important in the initiation and progression of dia- Loss of pericytes from retinal microvessels is an important event in the early stage of diabetic retinopathy, which is associated with increased pericyte apoptosis. Although the mechanisms responsible for pericyte apoptosis remain unclear, several studies have shown associations between dyslipidemia and the severity of diabetic retinopathy.1,2 Specifically, elevated levels of triglycerides, low density lipoprotein (LDL), and apolipoprotein B, a principal lipoprotein component of LDL, have been associated with diabetic retinopathy.1 However, these associations are relatively weak, leading us to hypothesize that the key contribution of lipoproteins to the propagation of diabetic retinopathy is not through changes in their plasma levels but, rather, through extravasation via a disrupted blood-retinal barrier and subsequent modification by glycation and oxidation. In support of this model, we have demonstrated that oxidized LDL is present in the retina in diabetic humans in proportion to the severity of diabetic retinopathy, 3 and in cell culture studies we have shown that oxidized LDL has injurious effects on retinal pericytes. 4,5

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“…Free iron in its Fe 3+ state will be reduced to Fe 2+ state by various agents like superoxide and ascorbate (12) and glucose induced reduction by NADPH dependent reactions (13). Existence of oxidative stress in diabetes is well proved by numerous studies (14). Previous studies have proved that poor glycemic control causes glycation of proteins and increased oxidative damage of proteins which are responsible for the diabetes related complications (15).…”

Section: Introductionmentioning

confidence: 99%

Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complications

Shetty

Prakash

Ibrahim

2008

Indian J Clin Biochem

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Free iron in serum has been found in several disease conditions including diabetes. In the present work, we studied the relationship between free iron, fasting blood glucose (FBG) and glycated haemoglobin (HbA 1c ). Study was carried out on 50 type 2 diabetes cases under poor glycemic control associated with complications, 53 type 2 diabetes cases under good glycemic control and 40 healthy controls. We estimated free iron, both ferrous (Fe +2 ) and ferric (Fe +3 ) form, protein thiols, lipid hydroperoxides, FBG, HbA 1c and serum ferritin levels in serum. There was a significant increase in free iron in Fe +3 state (p <0.01), HbA 1c (p<0.01), serum ferritin (p<0.01), lipid hydroperoxides (p<0.01) and significant decrease in protein thiols (<0.01) in diabetes cases under poor glycemic control compared to diabetes cases under good glycemic control and healthy controls. Free iron correlated positively with HbA 1c (p<0.01). Poor glycemic control and increase in glycation of haemoglobin is contributing to the increase in free iron pool which is known to increase oxidant generation.

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Serum markers of oxidative stress and severity of diabetic retinopathy.

Abstract: n e t t @ v i s i o n . e r i . h a rv a rd . e d u .

Cited by 138 publications

References 7 publications

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Tyrosine Nitration of Prostacyclin Synthase Is Associated with Enhanced Retinal Cell Apoptosis in Diabetes

Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complications

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