scholarly journals S-Allylmercapro-N-Acetylcysteine Attenuates the Oxidation-Induced Lens Opacification and Retinal Pigment Epithelial Cell Death In Vitro

Antioxidants ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Naphtali Savion ◽  
Samia Dahamshi ◽  
Milana Morein ◽  
Shlomo Kotev-Emeth
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Lens Opacity ◽  
Glutathione Level ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Lens Opacification

The capacity of S-Allylmercapto-N-acetylcysteine (ASSNAC) to protect human retinal pigment epithelial (RPE) cells (line ARPE-19) and porcine lenses from oxidative stress was studied. Confluent ARPE-19 cultures were incubated with ASSNAC or N-acetyl-cysteine (NAC) followed by exposure to oxidants and glutathione level and cell survival were determined. Porcine lenses were incubated with ASSNAC and then exposed to H2O2 followed by lens opacity measurement and determination of glutathione (reduced (GSH) and oxidized (GSSG)) in isolated lens adhering epithelial cells (lens capsule) and fiber cells consisting the lens cortex and nucleus (lens core). In ARPE-19 cultures, ASSNAC (0.2 mM; 24 h) increased glutathione level by 2–2.5-fold with significantly higher increase in GSH compared to NAC treated cultures. Similarly, ex-vivo exposure of lenses to ASSNAC (1 mM) significantly reduced the GSSG level and prevented H2O2 (0.5 mM)-induced lens opacification. These results demonstrate that ASSNAC up-regulates glutathione level in RPE cells and protects them from oxidative stress-induced cell death as well as protects lenses from oxidative stress-induced opacity. Further validation of these results in animal models may suggest a potential use for ASSNAC as a protective therapy in retinal degenerative diseases as well as in attenuation of oxidative stress-induced lens opacity.

scholarly journals Prevention of Oxidative Stress-Induced Retinal Pigment Epithelial Cell Death by the PPARγAgonist, 15-Deoxy-Delta 12, 14-ProstaglandinJ2

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Jason Y. Chang ◽  
Puran S. Bora ◽  
Nalini S. Bora
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Experimental Conditions ◽  
Pigment Epithelial ◽  
Age Related ◽  
Epithelial Cell Death

Cellular oxidative stress plays an important role in retinal pigment epithelial (RPE) cell death during aging and the development of age-related macular degeneration. Early reports indicate that during phagocytosis of rod outer segments, there is an increase of RPE oxidative stress and an upregulation of PPARγmRNA in these cells. These studies suggest that activation of PPARγmay modulate cellular oxidative stress. This paper presents a brief review of recent studies that investigate RPE oxidative stress under various experimental conditions. This is followed by a detailed review on those reports that examine the protective effect of the natural PPARγligand, 15d-PGJ2, against RPE oxidative stress. This agent can upregulate glutathione and prevent oxidant-induced intracellular reactive oxygen species accumulation, mitochondrial depolarization, and apoptosis. The cytoprotective effect of this agent, however, is not shared by other PPARγagonists. Nonetheless, this property of 15d-PGJ2may be useful in future development of pharmacological tools against retinal diseases caused by oxidative stress.

scholarly journals CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Céline Borras ◽  
Jérémie Canonica ◽  
Sylvie Jorieux ◽  
Toufik Abache ◽  
Mohamed El Sanharawi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Membrane Attack Complex ◽  
Retinal Pigment Epithelial Cells ◽  
Rpe Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

Abstract Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.

scholarly journals Sulforaphane Enhances the Ability of Human Retinal Pigment Epithelial Cell against Oxidative Stress, and Its Effect on Gene Expression Profile Evaluated by Microarray Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Liang Ye ◽  
Ting Yu ◽  
Yanqun Li ◽  
Bingni Chen ◽  
Jinshun Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Microarray Analysis ◽  
Retinal Pigment Epithelial ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Regulation Of Gene Expression ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Pigment Epithelial

To gain further insights into the molecular basis of Sulforaphane (SF) mediated retinal pigment epithelial (RPE) 19 cell against oxidative stress, we investigated the effects of SF on the regulation of gene expression on a global scale and tested whether SF can endow RPE cells with the ability to resist apoptosis. The data revealed that after exposure to H2O2, RPE 19 cell viability was increased in the cells pretreated with SF compared to the cell not treated with SF. Microarray analysis revealed significant changes in the expression of 69 genes in RPE 19 cells after 6 hours of SF treatment. Based on the functional relevance, eight of the SF-responsive genes, that belong to antioxidant redox system, and inflammatory responsive factors were validated. The up-regulating translation of thioredoxin-1 (Trx1) and the nuclear translocation of Nuclear factor-like2 (Nrf2) were demonstrated by immunoblot analysis in SF treated RPE cells. Our data indicate that SF increases the ability of RPE 19 cell against oxidative stress through up-regulating antioxidative enzymes and down-regulating inflammatory mediators and chemokines. The results suggest that the antioxidant, SF, may be a valuable supplement for preventing and retarding the development of Age Related Macular Degeneration.

scholarly journals Oxidative stress induces ferroptotic cell death in retinal pigment epithelial cells

2019 ◽  
Vol 181 ◽  
pp. 316-324 ◽  
Author(s):  
Kiyohito Totsuka ◽  
Takashi Ueta ◽  
Takatoshi Uchida ◽  
Murilo F. Roggia ◽  
Suguru Nakagawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

scholarly journals Collectin-11 Is an Important Modulator of Retinal Pigment Epithelial Cell Phagocytosis and Cytokine Production

2017 ◽  
Vol 9 (6) ◽  
pp. 529-545 ◽  
Author(s):  
Xia Dong ◽  
Weiju Wu ◽  
Liang Ma ◽  
Chengfei Liu ◽  
Mohajeet B. Bhuckory ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Retinal Pigment Epithelial ◽  
Cytokine Production ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Regulatory Protein ◽  
Phagocytic Cells ◽  
Rpe Cells ◽  
Cell Functions ◽  
Pigment Epithelial

In this paper, we report previously unknown roles for collectin-11 (CL-11, a soluble C-type lectin) in modulating the retinal pigment epithelial (RPE) cell functions of phagocytosis and cytokine production. We found that CL-11 and its carbohydrate ligand are expressed in both the murine and human neural retina; these resemble each other in terms of RPE and photoreceptor cells. Functional analysis of murine RPE cells showed that CL-11 facilitates the opsonophagocytosis of photoreceptor outer segments and apoptotic cells, and also upregulates IL-10 production. Mechanistic analysis revealed that calreticulin on the RPE cells is required for CL-11-mediated opsonophagocytosis whereas signal-regulatory protein α and mannosyl residues on the cells are involved in the CL-11-mediated upregulation of IL-10 production. This study is the first to demonstrate the role of CL-11 and the molecular mechanisms involved in modulating RPE cell phagocytosis and cytokine production. It provides a new insight into retinal health and disease and has implications for other phagocytic cells.

scholarly journals Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway

2015 ◽  
Vol 35 (11) ◽  
pp. 1952-1963 ◽  
Author(s):  
Jakub Hanus ◽  
Hongmei Zhang ◽  
David H. Chen ◽  
Qinbo Zhou ◽  
Peng Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Acetic Acid ◽  
Retinal Pigment Epithelial ◽  
Potent Inhibitor ◽  
Retinal Pigment ◽  
Pigment Epithelial ◽  
Antioxidative Response ◽  
Age Related ◽  
Gossypol Acetic Acid

The late stage of dry age-related macular degeneration (AMD), or geographic atrophy (GA), is characterized by extensive retinal pigment epithelial (RPE) cell death, and a cure is not available currently. We have recently demonstrated that RPE cells die from necrosis in response to oxidative stress, providing a potential novel mechanism for RPE death in AMD. In this study, we screened U.S. Food and Drug Administration-approved natural compounds and identified gossypol acetic acid (GAA) as a potent inhibitor of oxidative stress-induced RPE cell death. GAA induces antioxidative response and inhibits accumulation of excessive reactive oxygen species in cells, through which it prevents the activation of intrinsic necrotic pathway in response to oxidative stress. Sestrin2 (SESN2) is found to mediate GAA function in antioxidative response and RPE survival upon oxidative stress. Moreover, Forkhead box O3 transcription factor (FoxO3) is further found to be required for GAA-mediated SESN2 expression and RPE survival. Mechanistically, GAA promotes FoxO3 nuclear translocation and binding to theSESN2enhancer, which in turn increases its transcriptional activity. Taken together, we have identified GAA as a potent inhibitor of oxidative stress-induced RPE necrosis by regulating the FoxO3/SESN2 pathway. This study may have significant implications in the therapeutics of age-related diseases, especially GA.

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