N-Acetylcystein verbessert die lysosomale Funktion und beschleunigt den Abbau von Photorezeptoraußensegmenten in der RPE-Zellkultur

Schütt, F.; Völcker, Hans-Eberhard; Dithmar, Stefan

doi:10.1055/s-2007-963339

Cited by 6 publications

(3 citation statements)

References 22 publications

(25 reference statements)

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“…Therefore, limiting RPE oxidative stress may represent an effective way to slow or possibly reverse vision loss of patients due to diseases such as AMD. Indeed, several in vitro studies have shown that oxidative stress-related RPE cell death and dysfunction was improved when the cells were treated with antioxidants [73], [74], [75], [76]. Furthermore, a significant reduction toward retinal degeneration was reported in clinical trials involving AMD patients ingesting antioxidants such as lutein, zeaxanthin, zinc, vitamin C, and vitamin E [77], [78].…”

Section: Discussionmentioning

confidence: 99%

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

et al. 2013

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BackgroundDJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson’s disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress.MethodologyRetinal pigment epithelial (RPE) cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S) prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS) generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch’s membrane (BM)/choroid from AMD eyes.Principal FindingsDJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes.Conclusions/SignificanceDJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.

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Section: Discussionmentioning

confidence: 99%

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

et al. 2013

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“…Recently, pioneering proteomic profiling studies revealed the protein expressions in human RPE [21], drusen [22] and lipofuscin [23]. Other studies compared native differentiated to cultured dedifferentiated RPE cells [24,25].…”

Section: Discussionmentioning

confidence: 99%

Early biosignature of oxidative stress in the retinal pigment epithelium

Arnouk

Lee

Zhang

et al. 2011

Journal of Proteomics

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The retinal pigment epithelium (RPE) is essential for retinoid recycling and phagocytosis of photoreceptors. Understanding of proteome changes that mediate oxidative stress-induced degeneration of RPE cells may provide further insight into the molecular mechanisms of retinal diseases. In the current study, comparative proteomics has been applied to investigate global changes of RPE proteins under oxidative stress. Proteomic techniques including 2D SDS-PAGE, differential gel electrophoresis (DIGE) and tandem time-of-flight (TOF-TOF) mass spectrometry were used to identify early protein markers of oxidative stress in the RPE. Two biological models of RPE cells revealed several differentially-expressed proteins that are involved in key cellular processes such as energy metabolism, protein folding, redox homeostasis, cell differentiation, and retinoid metabolism. Our results provide a new perspective on early signaling molecules of redox imbalance in the RPE and putative therapeutic target proteins of RPE diseases caused by oxidative stress.

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“…Aufgrund dieses Wirkungsmechanismus wird Glutathion als Antioxidans zur Nahrungsergänzung genutzt. In der RPE-Zellkultur konnte man durch Zusatz von N-Acetylcystein das lysosomale Volumen und die korrespondierende Funktion deutlich verbessern [54]. Am Tiermodell konnte weiterhin gezeigt werden, dass Glutathionmangel zur Apoptoseinduktion in der Netzhaut führt [45].…”

Section: Glutathion N-acetylcysteinunclassified

Pathomechanismen der Alterung des RPE und prophylaktische Therapieoptionen im Hinblick auf die AMD

Schütt

Kopitz²,

Yu³

et al. 2008

Klin Monatsbl Augenheilkd

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An intact retinal pigment epithelium (RPE) represents an essential condition for the visual process. This post-mitotic RPE monolayer combines different functions such as degradation of photoreceptor outer segments, vitamin A cycle, support of retinal metabolism and maintenance of the outer blood-retina barrier. As a consequence of excessive metabolism, high oxygen levels, exposition to light of short wave length and ensuing radical formation, the RPE is highly dependent on protective systems. In spite of differentiated defence mechanisms, aging processes cause cumulative RPE damage, representing a major component of age-related macular degeneration (AMD), the leading cause of irreversible severe vision loss in people over 50 years old. A better understanding of the underlying pathophysiology will help to develop new prophylactic options which is becoming more and more important with increasing life expectancy.

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N-Acetylcystein verbessert die lysosomale Funktion und beschleunigt den Abbau von Photorezeptoraußensegmenten in der RPE-Zellkultur

Abstract: In our cell culture model of ROS fed RPE cells simulating aged RPE ACC improves lysosomal volume and metabolism. Therefore ACC may represent a new prophylactic and causal treatment option for AMD.

Cited by 6 publications

References 22 publications

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

Early biosignature of oxidative stress in the retinal pigment epithelium

Pathomechanismen der Alterung des RPE und prophylaktische Therapieoptionen im Hinblick auf die AMD

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