scholarly journals Caffeine Protects Against Retinal Inflammation

2022 ◽  
Vol 12 ◽  
Author(s):  
Federica Conti ◽  
Francesca Lazzara ◽  
Giovanni Luca Romano ◽  
Chiara Bianca Maria Platania ◽  
Filippo Drago ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Ischemia Reperfusion ◽  
Retinal Pigment ◽  
Pattern Electroretinogram ◽  
Retinal Pigment Epithelial Cells ◽  
Control Group ◽  
Sodium Fluorescein ◽  
Mrna Levels ◽  
Caffeine Treatment ◽  
Retinal Inflammation

Caffeine, one of the most consumed central nervous system (CNS) stimulants, is an antagonist of A1 and A2A adenosine receptors. In this study, we investigated the potential protective effects of this methylxanthine in the retinal tissue. We tested caffeine by using in vitro and in vivo paradigms of retinal inflammation. Human retinal pigment epithelial cells (ARPE-19) were exposed to lipopolysaccharide (LPS) with or without caffeine. This latter was able to reduce the inflammatory response in ARPE-19 cells exposed to LPS, attenuating the release of IL-1β, IL-6, and TNF-α and the nuclear translocation of p-NFκB. Additionally, caffeine treatment restored the integrity of the ARPE-19 monolayer assessed by transepithelial electrical resistance (TEER) and the sodium fluorescein permeability test. Finally, the ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to induce retinal inflammation and investigate the effects of caffeine treatment. Mouse eyes were treated topically with caffeine, and a pattern electroretinogram (PERG) was used to assess the retinal ganglion cell (RGC) function; furthermore, we evaluated the levels of IL-6 and BDNF in the retina. Retinal BDNF dropped significantly (p < 0.05) in the I/R group compared to the control group (normal mice); on the contrary, caffeine treatment maintained physiological levels of BDNF in the retina of I/R eyes. Caffeine was also able to reduce IL-6 mRNA levels in the retina of I/R eyes. In conclusion, these findings suggest that caffeine is a good candidate to counteract inflammation in retinal diseases.

Downregulation of the human taurine transporter by glucose in cultured retinal pigment epithelial cells

1999 ◽  
Vol 277 (4) ◽  
pp. E760-E771 ◽  
Author(s):  
Martin J. Stevens ◽  
Yoshiyuki Hosaka ◽  
Jennifer A. Masterson ◽  
Sandra M. Jones ◽  
Thommey P. Thomas ◽  
...  
Keyword(s):  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Prolonged Exposure ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Mrna Abundance ◽  
Retinal Pigment Epithelial Cells ◽  
Mrna Levels ◽  
Pigment Epithelial ◽  
Endogenous Antioxidant

In diabetes, activation of the aldose reductase (AR) pathway and alterations of glucose-sensitive signal transduction pathways have been implicated in depletion of intracellular taurine, an endogenous antioxidant and compatible osmolyte. Cellular taurine accumulation occurs by an osmotically induced, protein kinase C (PKC)-regulated Na+-taurine cotransporter (hTT). The effects of ambient glucose on taurine content, hTT activity, and hTT gene expression were therefore evaluated in low and high AR-expressing human retinal pigment epithelial cell lines. In low AR-expressing cells, 20 mM glucose decreased taurine content, hTT transporter activity, and mRNA levels, and these effects were unaffected by AR inhibition (ARI). In these cells, the inhibitory effects of high glucose on hTT appeared to be posttranscriptionally mediated, because 20 mM glucose decreased hTT mRNA stability without affecting hTT transcriptional rate. Inhibition of PKC overcame the decrease in hTT activity in high glucose-exposed cells. In high AR-expressing cells, prolonged exposure to 20 mM glucose resulted in intracellular taurine depletion, which paralleled sorbitol accumulation and was prevented by ARI. In these cells exposed to 5 mM glucose, hTT mRNA abundance was decreased and declined further in 20 mM glucose but was corrected by ARI. In 5 mM glucose, hTT transcriptional rate was markedly decreased in high AR-expressing cells, did not decline further in 20 mM glucose, but was increased by ARI to levels above those observed in low AR-expressing cells. Therefore, glucose rapidly and specifically decreases taurine content, hTT activity, and mRNA abundance by AR-unrelated and AR-related posttranscriptional and transcriptional mechanisms.

scholarly journals Analysis of Localization of Adult T-cell Leukemia-derived Factor in the Transient Ischemic Rat Retina After Treatment with OP-1206 α-CD, a Prostaglandin E1 Analogue

1997 ◽  
Vol 45 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Miho Yamamoto ◽  
Akihiro Ohira ◽  
Osamu Honda ◽  
Norihito Sato ◽  
Keizo Furuke ◽  
...  
Keyword(s):  
T Cell ◽  
Tissue Damage ◽  
Ischemia Reperfusion ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Prostaglandin E ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Oxygen Intermediates ◽  
Adult T Cell Leukemia

Prostaglandin E1 (PGE1) is commonly used in therapy for obstructive diseases, including ischemic retinopathy, in which pathogenetic reactive oxygen intermediates are responsible. However, the mechanism(s) of PGE1 in reducing tissue damage is still unclear. Adult T-cell leukemia-derived factor/human thioredoxin (ADF) is induced by oxidative stresses and has protective activity against oxidative cellular injury. To evaluate the possible involvement of ADF in the tissue-protective effect of PGE1, we analyzed ADF expression immunohistochemically using a rat transient retinal ischemia model. Rats were treated orally with 300 μg/kg/day OP-1206 α-cyclodextrin clathrate (OP-1206), a stable PGE1 analogue, for 14 days after photodynamic retinal vascular thrombosis by rose Bengal. Rats without any OP-1206 treatment were used as controls. In the OP-1206-treated rats, minimal retinal atrophy due to ischemia/reperfusion was observed histologically up to 14 days, whereas in the non-treated rats the inner layer of the retina became markedly atrophic. In parallel with the histological change, after 14 days following thrombosis ADF immunoreactivity was preserved on retinal pigment epithelial cells in the OP-1206-treated rats, whereas it was diminished in the non-treated rats. These findings suggest an important role for ADF in the OP-1206-dependent suppression of retinal tissue damage caused by oxidative insult.

scholarly journals C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qin Long ◽  
Xiaoguang Cao ◽  
Ailing Bian ◽  
Ying Li
Keyword(s):  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Mrna Level ◽  
Retinal Pigment Epithelial Cells ◽  
Mrna Levels ◽  
Sirna Duplex ◽  
Pigment Epithelial ◽  
Pathological Angiogenesis ◽  
Interfering Rna ◽  
Endothelial Growth Factor

Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis.

scholarly journals Piceatannol Protects Human Retinal Pigment Epithelial Cells against Hydrogen Peroxide Induced Oxidative Stress and Apoptosis through Modulating PI3K/Akt Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1515 ◽  
Author(s):  
Yiming Hao ◽  
Jie Liu ◽  
Ziyuan Wang ◽  
Liangli (Lucy) Yu ◽  
Jing Wang
Keyword(s):  
Hydrogen Peroxide ◽  
Nuclear Translocation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelium Cell ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Related Factor ◽  
Age Related

This study investigated the protective effect and the molecular mechanism of piceatannol on hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell (ARPE-19) damage. Piceatannol treatment significantly inhibited H2O2-induced RPE cell death and reactive oxygen species (ROS) generation by 64.4% and 75.0%, respectively. Results of flow cytometry showed that H2O2-induced ARPE-19 cells apoptosis was ameliorated by piceatannol supplementation, along with decreased relative protein expressions of Bax/Bcl-2, Cleave-Caspase-3, and Cleave-PARP. Moreover, piceatannol treatment induced NF-E2-related factor 2 (Nrf2) signaling activation, which was evidenced by increased transcription of anti-oxidant genes, glutamate-cysteine ligase catalytic subunit (GCLc), SOD, and HO-1. Knockdown of Nrf2 through targeted siRNA alleviated piceatannol-mediated HO-1 transcription, and significantly abolished piceatannol-mediated cytoprotection. LY294002 (PI3K inhibitor) dramatically blocked piceatannol-mediated increasing of Nrf2 nuclear translocation, HO-1 expression, and cytoprotective activity, indicating the involvement of PI3K/Akt pathway in the cytoprotective effect of piceatannol. The results from this suggest the potential of piceatannol in reducing the risk of age-related macular degeneration.

The Protective Effect of Genipin on Oxidative Stress Under Hypoxia and Hyperglycemia in Retinal Pigment Epithelial Cells

2021 ◽  
Vol 11 (11) ◽  
pp. 2239-2245
Author(s):  
Daifeng Wu ◽  
Yulin Wang ◽  
Yueyang Wu ◽  
Shujuan Ding
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Cell Viability ◽  
Retinal Pigment Epithelial ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Pi3k Inhibitor ◽  
Retinal Pigment Epithelial Cells ◽  
Rpe Cells ◽  
Pigment Epithelial

We aimed to explore the protective effect of genipin on retinal pigment epithelial (RPE) cells under hypoxia and hyperglycemia. RPE cells were cultured under hyperglycemia and hypoxia mimicking agent DFX. The cells were then exposed to genipin (10–50 μM), genipin + phospha-tidylinositol (3,4,5) trisphosphates (PIP3) as phosphoinositide 3-kinase (PI3K) inhibitor, and genipin+ PI3K agonist, followed by CCK-8 assay to detect the cell viability. Western blot determined PI3K/protein kinase B (AKT) pathway, and apoptosis- and anti-apoptosis-related proteins levels. MitoSOXTM Red kit was conducted to analyze reactive oxygen species (ROS) content. Finally, confocal immunofluorescence staining assessed nuclear translocation of Nuclear factor erythroid-derived 2-like 2 (Nrf2). Hyperglycemia and hypoxia treatment induced injury in RPE cells, with nuclear translocation of Nrf2 and ROS production. Importantly, administration of genipin alleviated the injury, up-regulated Bcl-2 expression, inhibited caspase-3 activity and nuclear translocation of Nrf2, and down-regulated the level of Bax and ROS. In addition, genipin pretreatment obviously increased PI3K and Akt phosphorylation and promoted cell proliferation and viability. On the contrary, PI3K inhibitor inactivated PI3K/AKT and decreased cell viability while PI3K agonist showed the opposite effect. Genipin prevented oxidative stress and apoptosis induced by hyperglycemia and hypoxia through PI3K/Akt signaling pathway.

scholarly journals Regulation of Matrix Metalloproteinase-2 Secretion from Scleral Fibroblasts and Retinal Pigment Epithelial Cells by miR-29a

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yingjie Zhang ◽  
Dan-Ning Hu ◽  
Yi Zhu ◽  
Hao Sun ◽  
Ping Gu ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Mrna Levels ◽  
Myopia Progression ◽  
Rpe Cells ◽  
Cell Expression

Purpose. To identify an effective method to prevent myopia progression by characterizing the regulation of matrix metalloproteinase- (MMP-) 2 expression and its secretion from scleral fibroblasts and retinal pigment epithelium (RPE) cells by miR-29a. Methods. The effects of miR-29a on the growth of scleral fibroblasts and RPE cells were assessed using the cell counting kit-8. The changes in MMP-2 mRNA levels in scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor were measured by quantitative PCR. Enzyme-linked immunosorbent assays were used to determine the changes in MMP-2 secretion from scleral fibroblasts and RPE cells after transfection with miR-29a mimics or inhibitor. Results. The miR-29a mimics or inhibitor did not significantly alter the growth of scleral fibroblasts or RPE cells at 24, 48, or 72 hours after transfection. MMP-2 mRNA levels were significantly decreased in scleral fibroblasts and RPE cells transfected with the miR-29a mimics. The secretion of MMP-2 by scleral fibroblasts and RPE cells was significantly decreased in cells transfected with the miR-29a mimics. Conclusions. Suppression of scleral fibroblast and RPE cell expression and secretion of MMP-2 by miR-29a can be used as a therapeutic target for the prevention and treatment of myopia.

scholarly journals Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1

2020 ◽  
Vol 21 (10) ◽  
pp. 3716 ◽  
Author(s):  
Josué Rivera-Pérez ◽  
Martín Martínez-Rosas ◽  
César A. Conde-Castañón ◽  
Julia D. Toscano-Garibay ◽  
Nancy J. Ruiz-Pérez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protective Effect ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion ◽  
Neuronal Cells ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna Levels ◽  
Neuroprotective Efficacy

Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0–30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression.

Fucoidan reduces inflammatory response in a rat model of hepatic ischemia–reperfusion injury

2015 ◽  
Vol 93 (11) ◽  
pp. 999-1005 ◽  
Author(s):  
Xiao-jing Li ◽  
Qi-fa Ye
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cell ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Sulfated Polysaccharides ◽  
Control Group ◽  
Mrna Levels ◽  
Inflammatory Signaling

Ischemia–reperfusion (I/R) injury after a liver transplant is a major cause of severe complications that lead to graft dysfunction. Fucoidan, a complex of sulfated polysaccharides derived from marine brown algae, demonstrated antiapoptotic as well as potential anti-inflammatory properties in previous studies. Fucoidan has also shown protective effects on I/R-injured kidney and heart. However, whether fucoidan can attenuate hepatic I/R injury has not been examined. To clarify the role of fucoidan in hepatic I/R injury, Sprague–Dawley rats were subjected to sham operation or ischemia followed by reperfusion with treatment of saline or fucoidan (50, 100, or 200 mg·(kg body mass)−1·d−1). The fucoidan-treated group showed decreased levels of alanine aminotransferase and aspartate aminotransferase compared with the control group. Myeloperoxidase and malondialdehyde activities and mRNA levels of CD11b in the fucoidan-treated group were significantly decreased. Hepatocellular swelling/necrosis, sinusoidal/vascular congestion, and inflammatory cell infiltration were also attenuated in the fucoidan group. The expression of TNF-α, IL-6, IL-1β, CXCL-10, VCAM-1, and ICAM-1 were markedly decreased in the samples from the fucoidan-treated group. Fucoidan largely prevented activation of the inflammatory signaling pathway, compared with the control group. In summary, fucoidan can protect the liver from I/R injury through suppressing activation of the inflammatory signaling pathway, as well as the expression of inflammatory mediators, and inflammatory cell infiltration.

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