The Oxidative Stress and Mitochondrial Dysfunction during the Pathogenesis of Diabetic Retinopathy

Wu, Meng‐Yu; Yiang, Giou‐Teng; Lai, Tzu-Ting; Li, Chia‐Jung

doi:10.1155/2018/3420187

Cited by 158 publications

(136 citation statements)

References 129 publications

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“…Oxidative stress though being closely interlinked to inflammation, could also be the cumulative effect of continued insults to the eye such as ischemia and hyperglycemia [20]. To further quantitate the underlying oxidative stress and inflammation in membrane formation and DR pathogenesis, a targeted gene expression profiling was undertaken by semi-quantitative real time PCR using SYBR green chemistry.…”

Section: Gene Expression Analysis Of Oxidative Stress and Inflammatiomentioning

confidence: 99%

Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation

et al. 2020

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Fibrocellular membrane or epiretinal membrane (ERM) forms on the surface of the inner limiting membrane (ILM) in the inner retina and alters the structure and function of the retina. ERM formation is frequently observed in ocular inflammatory conditions, such as proliferative diabetic retinopathy (PDR) and retinal detachment (RD). Although peeling of the ERM is used as a surgical intervention, it can inadvertently distort the retina. Our goal is to design alternative strategies to tackle ERMs. As a first step, we sought to determine the composition of the ERMs by identifying the constituent cell-types and gene expression signature in patient samples. Using ultrastructural microscopy and immunofluorescence analyses, we found activated microglia, astrocytes, and Müller glia in the ERMs from PDR and RD patients. Moreover, oxidative stress and inflammation associated gene expression was significantly higher in the RD and PDR membranes as compared to the macular hole samples, which are not associated with inflammation. We specifically detected differential expression of hypoxia inducible factor 1-α (HIF1-α), proinflammatory cytokines, and Notch, Wnt, and ERK signaling pathway-associated genes in the RD and PDR samples. Taken together, our results provide new information to potentially develop methods to tackle ERM formation.

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Section: Gene Expression Analysis Of Oxidative Stress and Inflammatiomentioning

confidence: 99%

Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation

et al. 2020

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“…Among several mechanisms of CDDP-induced renal damage, oxidative stressmediated nephrotoxicity is significant. The overproduction of ROS can induce inflammation, mitochondrial dysfunction and cell apoptosis (Reuter et al, 2010;Wu et al, 2018). Therefore, counteracting the environmental stress caused by these reactive species can further inhibit inflammation and apoptosis and thus play a protective role in CDDP-induced renal injury.…”

Section: Introductionmentioning

confidence: 99%

Isoorientin Attenuates Cisplatin-Induced Nephrotoxicity Through the Inhibition of Oxidative Stress and Apoptosis via Activating the SIRT1/SIRT6/Nrf-2 Pathway

et al. 2020

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Cisplatin (CDDP) is a widely used chemotherapeutic agent for various solid tumors, but its severe side effects, particularly nephrotoxicity, limit its clinical application. Isoorientin (Iso) is a flavonoid-like compound known to have antioxidant effects. As oxidative injury plays a vital role in CDDP-induced acute kidney injury (AKI), the effect of Iso on CDDPinduced nephrotoxicity has not yet been researched. We assessed the effects of Iso against CDDP-induced nephrotoxicity in vitro using mTEC cells and further explored the mechanisms underlying CDDP-induced renal dysfunction in vivo in WT and Nrf2 −/− mice. The results showed that Iso treatment significantly reduced CDDP-induced nephrotoxicity via attenuating cell damage in vitro and via ameliorating renal injury, as determined by biochemical markers, in mice. The molecular mechanism underlying this protection was also investigated. Iso up-regulated the expression levels of SIRT1 and SIRT6 in vivo and in vitro. In addition, Iso activated Nrf2 translocation and the expression levels of its downstream antioxidant enzymes, such as HO-1 and NQO1, whereas it inhibited the expression level of NOX4, thus decreasing oxidative stress. Notably, the protective effects of Iso observed in WT mice were completely abolished in Nrf2 −/− mice. Collectively, these data indicate that the protective effect of Iso on CDDP-induced nephrotoxicity by SIRT1-and SIRT6-mediated Nrf2 activation regulates oxidative stress, inflammation and apoptosis. The absence of Nrf2 exacerbates CDDP-induced renal damage, and the pharmacological activation of Nrf2 may represent a novel therapy to prevent kidney injury.

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“…It develops through a series of stages of increasing degrees of severity [14] and affects the microvascular circulation of the retina, compromising the integrity and function of retinal tissue. Endothelial cells, the building blocks of the microvasculature, are particularly sensitive to sustained hyperglycemia-induced damage [15,16]. The retina is not only a network of blood vessels, rather it is a multilayered neuronal (photoreceptors, and horizontal, bipolar, amacrine and ganglion cells) and glial (astrocytes, Müller cells, and microglia) cells that covers approximately 95% of the tissue, with blood vessels (endothelial cells and pericytes) comprising only a small portion (<5%) [17].…”

Section: Pathophysiologic Changes and Clinical Definition Of Drmentioning

confidence: 99%

Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy

et al. 2020

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Diabetic retinopathy (DR) is a complex, progressive, and heterogenous retinal degenerative disease associated with diabetes duration. It is characterized by glial, neural, and microvascular dysfunction, being the blood-retinal barrier (BRB) breakdown a hallmark of the early stages. In advanced stages, there is formation of new blood vessels, which are fragile and prone to leaking. This disease, if left untreated, may result in severe vision loss and eventually legal blindness. Although there are some available treatment options for DR, most of them are targeted to the advanced stages of the disease, have some adverse effects, and many patients do not adequately respond to the treatment, which demands further research. Oxidative stress and low-grade inflammation are closely associated processes that play a critical role in the development of DR. Retinal cells communicate with each other or with another one, using cell junctions, adhesion contacts, and secreted soluble factors that can act in neighboring or long-distance cells. Another mechanism of cell communication is via secreted extracellular vesicles (EVs), through exchange of material. Here, we review the current knowledge on deregulation of cell-to-cell communication through EVs, discussing the changes in miRNA expression profiling in body fluids and their role in the development of DR. Thereafter, current and promising therapeutic agents for preventing the progression of DR will be discussed.

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The Oxidative Stress and Mitochondrial Dysfunction during the Pathogenesis of Diabetic Retinopathy

Cited by 158 publications

References 129 publications

Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation

Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation

Isoorientin Attenuates Cisplatin-Induced Nephrotoxicity Through the Inhibition of Oxidative Stress and Apoptosis via Activating the SIRT1/SIRT6/Nrf-2 Pathway

Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy

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