Toxic effects of A2E in human ARPE-19 cells were prevented by resveratrol: a potential nutritional bioactive for age-related macular degeneration treatment

Alaimo, Agustina; Santo, Mariana Carolina Di; Rubio, Ana Paula Domínguez; Chaufan, Gabriela; Liñares, Guadalupe García; Pérez, Oscar E.

doi:10.1007/s00204-019-02637-w

Cited by 27 publications

(26 citation statements)

References 101 publications

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“…In addition, ZIKV preferentially infects Müller and RPE cells, impairing their neurotrophic functions, and eliciting retinal inflammatory responses (Zhao et al, 2017). Notably, the RPE localized in the macular area lies in a high oxidative environment, because of its high metabolic demand, reactive oxygen species (ROS) levels, blood flow and mitochondria content (Moine et al, 2018;Dieguez et al, 2019;Alaimo et al, 2020). The permissiveness of the RPE to viral infections makes it a pertinent tissue to explore the host-cell interactions (Simonin et al, 2019).…”

Section: Zikv Infection Disturbs Mitochondrial Dynamicsmentioning

confidence: 99%

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

et al. 2020

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Zika virus (ZIKV) is an enveloped positive stranded RNA virus belonging to the genus Flavivirus in the family Flaviviridae that emerged in recent decades causing pandemic outbreaks of human infections occasionally associated with severe neurological disorders in adults and newborns. The intracellular steps of flavivirus multiplication are associated to cellular membranes and their bound organelles leading to an extensive host cell reorganization. Importantly, the association of organelle dysfunction with diseases caused by several human viruses has been widely reported in recent studies. With the aim to increase the knowledge about the impact of ZIKV infection on the host cell functions, the present study was focused on the evaluation of the reorganization of three cell components, promyelocytic leukemia nuclear bodies (PML-NBs), mitochondria, and lipid droplets (LDs). Relevant human cell lines including neural progenitor cells (NPCs), hepatic Huh-7, and retinal pigment epithelial (RPE) cells were infected with the Argentina INEVH116141 ZIKV strain and the organelle alterations were studied by using fluorescent cell imaging analysis. Our results have shown that these three organelles are targeted and structurally modified during ZIKV infection. Considering the nuclear reorganization, the analysis by confocal microscopy of infected cells showed a significantly reduced number of PML-NBs in comparison to uninfected cells. Moreover, a mitochondrial morphodynamic perturbation with an increased fragmentation and the loss of mitochondrial membrane potential was observed in ZIKV infected RPE cells. Regarding lipid structures, a decrease in the number and volume of LDs was observed in ZIKV infected cells. Given the involvement of these organelles in host defense processes, the reported perturbations may be related to enhanced virus replication through protection from innate immunity. The understanding of the cellular remodeling will enable the design of new host-targeted antiviral strategies.

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Section: Zikv Infection Disturbs Mitochondrial Dynamicsmentioning

confidence: 99%

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

et al. 2020

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“…Resveratrol-induced autophagy is also associated with the rescue of NRF-2, which is involved in autophagy-related mitophagy and mitochondriogenesis, protection from oxidative stress, and caspase-related apoptosis, as well as downregulation of NF-κB, NLRP3, and pro-inflammatory cytokines production [ 203 , 206 , 207 , 208 , 209 , 210 , 211 ]. Within RPE cells, resveratrol prevents A2E-induced mitochondrial network fragmentation [ 212 ], and it also suppresses VEGF secretion induced by inflammatory cytokines [ 213 ]. Remarkably, the administration of a resveratrol-rich formulation rescues the autophagy flux, to provide cytoprotection against either proteasome inhibition or chloroquine/hydroquinone exposure in RPE cells [ 59 , 214 , 215 ].…”

Section: Lutein Resveratrol and Vaccinium Myrtillus mentioning

confidence: 99%

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

Pinelli

Biagioni

Limanaqi

et al. 2020

IJMS

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Which pathogenic mechanisms underlie age-related macular degeneration (AMD)? Are they different for dry and wet variants, or do they stem from common metabolic alterations? Where shall we look for altered metabolism? Is it the inner choroid, or is it rather the choroid–retinal border? Again, since cell-clearing pathways are crucial to degrade altered proteins, which metabolic system is likely to be the most implicated, and in which cell type? Here we describe the unique clearing activity of the retinal pigment epithelium (RPE) and the relevant role of its autophagy machinery in removing altered debris, thus centering the RPE in the pathogenesis of AMD. The cell-clearing systems within the RPE may act as a kernel to regulate the redox homeostasis and the traffic of multiple proteins and organelles toward either the choroid border or the outer segments of photoreceptors. This is expected to cope with the polarity of various domains within RPE cells, with each one owning a specific metabolic activity. A defective clearance machinery may trigger unconventional solutions to avoid intracellular substrates’ accumulation through unconventional secretions. These components may be deposited between the RPE and Bruch’s membrane, thus generating the drusen, which remains the classic hallmark of AMD. These deposits may rather represent a witness of an abnormal RPE metabolism than a real pathogenic component. The empowerment of cell clearance, antioxidant, anti-inflammatory, and anti-angiogenic activity of the RPE by specific phytochemicals is here discussed.

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“…Various studies based on ARPE-19 cell line present pharmacological solution to retinal dystrophies. The same cell line is also used to identify new candidate compounds able to protect RPE against A2E oxidation [26]. As highlighted in the manuscript, the treatment with such a compound determines relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration.…”

Section: Introductionmentioning

confidence: 99%

Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

et al. 2020

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Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes’ profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

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Toxic effects of A2E in human ARPE-19 cells were prevented by resveratrol: a potential nutritional bioactive for age-related macular degeneration treatment

Cited by 27 publications

References 101 publications

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals

Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

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