TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

Devi, Takhellambam S.; Lee, Icksoo; Hüttemann, Maik; Kumar, Ashok; Nantwi, Kwaku D.; Singh, Lalit P.

doi:10.1155/2012/438238

Cited by 175 publications

(225 citation statements)

References 69 publications

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“…Given the relevance of the retina as a target tissue in diabetes, it is not surprising that TXNIP and the inflammasome have been found to contribute to the pathogenesis of diabetic retinopathy (Devi et al, 2012). Very interestingly, the inflammasome appears to be also involved in ischemia-dependent injury of retinal ganglion cells via a panx-1-mediated process, as shown by the observation that panx-1 2/2 mice are protected.…”

Section: G Retinopathiesmentioning

confidence: 99%

The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors

2013

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Section: G Retinopathiesmentioning

confidence: 99%

The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors

2013

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“…Thioredoxin-interacting protein (TXNIP) has recently been described as another potential gene target for preventing neovascular injury/cell death and the pathogenesis of DR (Devi et al, 2012). TXNIP is significantly increased in the diabetic rat retina (Perrone et al, 2009) and causes proinflammatory gene expression of VEGFA, COX-2, Intercellular Adhesion Molecule 1 and sclerotic fibronectin (Perrone et al, 2009;Sbai et al, 2010).…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Guzmán-Aránguez

Loma

Pintor

2013

British J Pharmacology

110

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RNA interference (RNAi) can be used to inhibit the expression of specific genes in vitro and in vivo, thereby providing an extremely useful tool for investigating gene function. Progress in the understanding of RNAi-based mechanisms has opened up new perspectives in therapeutics for the treatment of several diseases including ocular disorders. The eye is currently considered a good target for RNAi therapy mainly because it is a confined compartment and, therefore, enables local delivery of small-interfering RNAs (siRNAs) by topical instillation or direct injection. However, delivery strategies that protect the siRNAs from degradation and are suitable for long-term treatment would be help to improve the efficacy of RNAi-based therapies for ocular pathologies. siRNAs targeting critical molecules involved in the pathogenesis of glaucoma, retinitis pigmentosa and neovascular eye diseases (age-related macular degeneration, diabetic retinopathy and corneal neovascularization) have been tested in experimental animal models, and clinical trials have been conducted with some of them. This review provides an update on the progress of RNAi in ocular therapeutics, discussing the advantages and drawbacks of RNAi-based therapeutics compared to previous treatments. AbbreviationsAMD, age-related macular degeneration; Apaf-1, apoptotic protease-activating factor-1; CNV, choroidal neovascularization; CTGF, connective tissue growth factor; DR, diabetic retinopathy; dsRNA, double-stranded RNA; ECM, extracellular matrix; HIF-1α, hypoxia-inducible factor-1α; IOP, intraocular pressure; ONC, optic nerve crush; POAG, open-angle glaucoma; RGC, retinal ganglion cell; RISC, RNA-induced silencing complex; RNAi, RNA interference; RP, retinitis pigmentosa; Smad, signalling mathers against decapentaplegic; SPARC, secreted protein acidic and rich in cysteine; TLR3, toll-like receptor 3; TM, trabecular meshwork; TXNIP, thioredoxin interacting protein IntroductionRNA interference (RNAi) technology has been used to elucidate gene function, to generate model systems and to identify new molecular targets. In addition, RNAi is currently progressing from basic research to potential therapeutic applications. Because any gene that causes or contributes to a disease is susceptible to suppression by RNAi, RNAi therapy represents a promising biomedical strategy for treating a diverse range of diseases including cancer, cardiovascular diseases, neurodegenerative diseases, inflammatory conditions, viral infections and ocular diseases (Guo et al., 2010). In particular, the accessibility of the eye facilitates small-interfering RNA (siRNA) delivery, and naked siRNA has been efficiently applied by topical administration to the anterior segment or by intravitreal injection to the posterior segment (de Fougerolles, 2008). As the localized delivery of siRNA to the eye is less challenging than for other tissues, there has been significant progress made towards its use as a therapeutic procedure for eye diseases. In fact, several siRNA-based therapeutic agents for o...

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“…In rat experimental model of diabetes, hyperglycemic state had induced Txnip expression which has been implicated with increased inflammation and gliosis [70]. It has been suggested nitric oxide blocks expression of the Txnip improving thioredoxin activity [71].…”

Section: Molecular Pathways Of Diabetes Mellitus Pathogenesismentioning

confidence: 99%

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

Ferrari¹

2017

Integr Obesity Diabetes

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Oxidative and nitrosative stress reactions are implicated in cell and organ damage due to diabetes mellitus. In both type 1 and type 2 DM there is a massive oxidative and nitrosative stresses which have been associated with intensive changes on both antioxidant enzyme systems (SOD, CAT, GPx, GSH) and total antioxidant capacity (TAC) causing peroxidative damage to lipids, proteins, nucleic acids and carbohydrates which can be used as DM biomarkers. Molecular pathophysiology of diabetes mellitus envolves induction of the the NFkB and p38-MAPK cell signaling pathways by Rac, TNF-α, TLR4, decrease of antioxidant defenses, and direct mitochondrial damage. Knowledge of molecular pathways is essential for research of newer preventive and therapeutic approaches in diabetes mellitus complications (atherosclerosis, myocardial damage, endothelial dysfunction, and renal failure).urine, feces, tissue sample), vegetable or fruit extract or even foods or pharmaceuticals [14][15][16].This article review and update the clinical, cellular, and molecular knowledge of free radicals and antioxidant defenses in diabetes mellitus. Ethiopathogenesis of diabetes mellitus I and IIDiabetes mellitus has been conceptualized as a group of metabolic disorders characterized by hyperglicemia as a result of insulin secretion failure and/or lacking of insulin action on target cells. The chronic diabetic hyperglicemic state has been related to long-term organ damage especially to the heart, endothelium and blood vessels, nerves, kidney, and eyes [17][18][19].

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TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

Cited by 175 publications

References 69 publications

The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors

The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors

Small‐interfering RNAs (siRNAs) as a promising tool for ocular therapy

Antioxidant defenses in diabetes mellitus: a clinical and molecular approach

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