scholarly journals Antiviral Bioactivity of Resveratrol Against Zika Virus Infection in Human Retinal Pigment Epithelial Cells

2021 ◽  
Author(s):  
Constanza Andrea Russo ◽  
Maria Florencia Torti ◽  
Agostina Belén Márquez ◽  
Claudia Soledad Sepúlveda ◽  
Agustina Alaimo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Zika Virus ◽  
Retinal Pigment Epithelial ◽  
Mitochondrial Dynamics ◽  
Retinal Pigment ◽  
Antiviral Agent ◽  
Retinal Pigment Epithelial Cells ◽  
Protective Effects ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

Abstract Resveratrol (RES) is a polyphenol with increasing interest for its inhibitory effects on a wide variety of viruses. Zika virus (ZIKV) is an arbovirus of the Flaviviridae family for which there is no approved treatment or vaccine, and which has become a major global health threat. Within the broad spectrum of ophthalmological manifestations after infection, retinal pigment epithelial cells (RPE) type is one of the most permissive and susceptible to the virus. This work explored the protective effects of RES on ZIKV-infected human RPE cells. RES treatment resulted in a significant reduction of infectious viral titer in infected male ARPE-19 and female hTERT-RPE1 cells. This protection was positively influenced by the action of RES on mitochondrial dynamics, restoring the ZIKV induced fragmentation of mitochondrial network to conditions similar to those of uninfected control cultures. Also, docking studies showed that RES has a high affinity for two enzymes of the rate-limiting steps of pyrimidine and purine biosynthesis and viral polymerase. In conclusion, our findings indicated that RES could be considered as an antiviral agent to treat ZIKV-induced ocular abnormalities.

scholarly journals Suppression of PGC-1α Drives Metabolic Dysfunction in TGFβ2-Induced EMT of Retinal Pigment Epithelial Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4701
Author(s):  
Daisy Y. Shu ◽  
Erik R. Butcher ◽  
Magali Saint-Geniez
Keyword(s):  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Transforming Growth Factor ◽  
Citrate Synthase ◽  
Mitochondrial Dynamics ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Mesenchymal Transition ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

PGC-1α, a key orchestrator of mitochondrial metabolism, plays a crucial role in governing the energetically demanding needs of retinal pigment epithelial cells (RPE). We previously showed that silencing PGC-1α induced RPE to undergo an epithelial-mesenchymal-transition (EMT). Here, we show that induction of EMT in RPE using transforming growth factor-beta 2 (TGFβ2) suppressed PGC-1α expression. Correspondingly, TGFβ2 induced defects in mitochondrial network integrity with increased sphericity and fragmentation. TGFβ2 reduced expression of genes regulating mitochondrial dynamics, reduced citrate synthase activity and intracellular ATP content. High-resolution respirometry showed that TGFβ2 reduced mitochondrial OXPHOS levels consistent with reduced expression of NDUFB5. The reduced mitochondrial respiration was associated with a compensatory increase in glycolytic reserve, glucose uptake and gene expression of glycolytic enzymes (PFKFB3, PKM2, LDHA). Treatment with ZLN005, a selective small molecule activator of PGC-1α, blocked TGFβ2-induced upregulation of mesenchymal genes (αSMA, Snai1, CTGF, COL1A1) and TGFβ2-induced migration using the scratch wound assay. Our data show that EMT is accompanied by mitochondrial dysfunction and a metabolic shift towards reduced OXPHOS and increased glycolysis that may be driven by PGC-1α suppression. ZLN005 effectively blocks EMT in RPE and thus serves as a novel therapeutic avenue for treatment of subretinal fibrosis.

scholarly journals Cyanidin-3-glucoside Alleviates 4-Hydroxyhexenal-Induced NLRP3 Inflammasome Activation via JNK-c-Jun/AP-1 Pathway in Human Retinal Pigment Epithelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaolu Jin ◽  
Chengtao Wang ◽  
Wei Wu ◽  
Tingting Liu ◽  
Baoping Ji ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nlrp3 Inflammasome ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Pigment Epithelial ◽  
Nlrp3 Inflammasome Activation ◽  
Pigment Epithelial Cells

Recently, the NLRP3 inflammasome activation in the eyes has been known to be associated with the pathogenesis of age-related macular degeneration. The aim of this study was to investigate the protective effects of cyanidin-3-glucoside (C3G), an important anthocyanin with great potential for preventing eye diseases, against 4-hydroxyhexenal- (HHE-) induced inflammatory damages in human retinal pigment epithelial cells, ARPE-19. We noticed that C3G pretreatment to the ARPE-19 cells rescued HHE-induced antiproliferative effects. Cell apoptosis ratio induced by HHE was also decreased by C3G, measured by flow cytometry. The activation of NLRP3 inflammasome induced by HHE was found with increases of caspase-1 activity, proinflammatory cytokine releases (IL-1β and IL-18), and NLRP3 inflammasome-related gene expressions (NLRP3, IL-1β, IL-18, and caspase-1). The C3G showed potent inhibitive effects on these NLRP3 inflammasome activation hallmarks induced by HHE. Moreover, we noticed that the C3G’s pretreatment leads to a delayed and a decreased JNK activation in HHE-challenged ARPE-19 cells. Finally, using a luciferase reporter gene assay system, we demonstrated that HHE-induced activation protein- (AP-) 1 transcription activity was abolished by C3G pretreatment in a dose-dependent manner. Taken together, these data showed that HHE leads to inflammatory damages to ARPE-19 cells while C3G has great protective effects, highlighting future potential applications of C3G against AMD-associated inflammation.

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