Abnormalities of Retinal Metabolism in Diabetes or Experimental Galactosemia. IV. Antioxidant Defense System

Kowluru, Renu A.; Kern, Timothy S.; Engerman, Ronald L.

doi:10.1016/s0891-5849(96)00347-4

Cited by 157 publications

(148 citation statements)

References 23 publications

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“…Although no retinal histology data have been published for diabetic PKC b knockout mice to date, in clinical trials of the drug ruboxistaurin, a PKC b inhibitor, only relatively modest outcomes were found (62). Many of the effective treatments in Table 3 are in line with the notion that diabetes is linked to upregulation of oxidative stress and inflammation factors (63,64). The treatments evaluated in Table 3 were given at the start of diabetes (i.e.…”

Section: Dpomentioning

confidence: 87%

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

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There is a pressing need for retina-specific imaging biomarkers that robustly measure early (subclinical) changes in physiology, are linked to the histopathology responsible for vision loss, and, importantly, predict treatment efficacy. This review focuses on the following four MRI markers that we have developed and applied in preclinical and clinical settings: preretinal vitreous oxygen level (a steady-state biomarker of inner retinal oxygen tension); leakage of contrast agent into the vitreous (a steady-state biomarker of blood-retinal barrier permeability surface area product); change in preretinal vitreous oxygen tension during a hyperoxic provocation (a functional biomarker of vascular autoregulation); and retinal uptake of systemically administered manganese during a visual task (a functional biomarker of intraretinal ion regulation). We conclude that functional biomarkers are most promising for prognostic evaluation of treatment efficacy earlier in the course of retinopathy than is currently possible.

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Section: Dpomentioning

confidence: 87%

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Berkowitz

Roberts

2008

NMR in Biomedicine

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“…Retinal superoxide levels are elevated (7), mRNA levels of superoxide dismutase are downregulated (21), and glutathione levels are decreased in diabetes (22), suggesting an overwhelming of the endogenous defense system. The therapies that inhibit superoxide dismutase activity and superoxide production and decrease retinal glutathione levels also inhibit the development of diabetic retinopathy (7,23). In addition, we have shown that in diabetes, retinal mitochondria experience dysfunction, and inhibition of superoxide accumulation inhibits the apoptosis of retinal capillary cells (6).…”

Section: Discussionmentioning

confidence: 99%

Effect of Long-Term Administration of α-Lipoic Acid on Retinal Capillary Cell Death and the Development of Retinopathy in Diabetic Rats

Kowluru

Odenbach²

2004

Diabetes

220

229

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Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. ␣-Lipoic acid, a thiol antioxidant, has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerve, kidney, and retina. The purpose of this study was to examine the effect of ␣-lipoic acid on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without ␣-lipoic acid (400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of ␣-lipoic acid administration on retinal 8-hydroxy-2deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. ␣-Lipoic acid administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the two diabetic groups (with and without ␣-lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over twofold and 70%, respectively, in diabetes, and ␣-lipoic acid administration inhibited these increases. Our results demonstrate that the long-term administration of ␣-lipoic acid has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. ␣-Lipoic acid supplementation represents an achievable adjunct therapy to help prevent vision loss in diabetic patients. Diabetes 53

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“…While intimately linked with AGE formation, oxidative imbalances in diabetic retinopathy have also been widely reported (23)(24)(25)(26). Vitamin E (VE) can cause normalization of diabetes-related retinal blood flow abnormalities (27), while this antioxidant, in combination with vitamin C, can inhibit capillary cell death (28).…”

mentioning

confidence: 99%

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

et al. 2002

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We examined the ability of pyridoxamine (PM), an inhibitor of formation of advanced glycation end products (AGEs) and lipoxidation end products (ALEs), to protect against diabetes-induced retinal vascular lesions. The effects of PM were compared with the antioxidants vitamin E (VE) and R-␣-lipoic acid (LA) in streptozotocin-induced diabetic rats. Animals were given either PM (1 g/l drinking water), VE (2,000 IU/kg diet), or LA (0.05%/kg diet). After 29 weeks of diabetes, retinas were examined for pathogenic changes, alterations in extracellular matrix (ECM) gene expression, and accumulation of the immunoreactive AGE/ALE N -(carboxymethyl)lysine (CML). Acellular capillaries were increased more than threefold, accompanied by significant upregulation of laminin immunoreactivity in the retinal microvasculature. Diabetes also increased mRNA expression for fibronectin (2-fold), collagen IV (1.6-fold), and laminin ␤ chain (2.6-fold) in untreated diabetic rats compared with nondiabetic rats. PM treatment protected against capillary drop-out and limited laminin protein upregulation and ECM mRNA expression and the increase in CML in the retinal vasculature. VE and LA failed to protect against retinal capillary closure and had inconsistent effects on diabetes-related upregulation of ECM mRNAs. These results indicate that the AGE/ALE inhibitor PM protected against a range of pathological changes in the diabetic retina and may be useful for treating diabetic retinopathy.

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Abnormalities of Retinal Metabolism in Diabetes or Experimental Galactosemia. IV. Antioxidant Defense System

Cited by 157 publications

References 23 publications

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Prognostic MRI biomarkers of treatment efficacy for retinopathy

Effect of Long-Term Administration of α-Lipoic Acid on Retinal Capillary Cell Death and the Development of Retinopathy in Diabetic Rats

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

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