scholarly journals Fallopia Japonica and Prunella Vulgaris Inhibit Myopia Progression by Suppressing Akt and NFκB Mediated Inflammatory Reactions

2021 ◽  
Author(s):  
Chia-Hung Lin ◽  
Chih-Sheng Chen ◽  
Yao-Chien Wang ◽  
En-Shyh Lin ◽  
Ching-Yao Chang ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Axial Length ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Retinal Pigment Epithelial Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Myopia Progression ◽  
Rpe Cells ◽  
Expression Levels

The increased global incidence of myopia requires the establishment of therapeutic approaches. Previous studies have suggested that inflammation plays an important role in the development and progression of myopia. We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJE and PVE lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. Expression levels of IL-6, IL-8, and TNF-α were upregulated in retinal pigment epithelium (RPE) cells treated with IL-6 and TNF-α. FJ extract (FJE) + PV extract (PVE) reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-β1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type Ⅰ collagen expression. Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

scholarly journals Effect of Combined Treatment With Fallopia Japonica and Prunella Vulgaris Extract on Myopia Progress

2021 ◽  
Author(s):  
Chia-Hung Lin ◽  
Chih-Sheng Chen ◽  
Yao-Chien Wang ◽  
En-Shyh Lin ◽  
Ching-Yao Chang ◽  
...  
Keyword(s):  
Axial Length ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Retinal Pigment ◽  
Combined Treatment ◽  
Prunella Vulgaris ◽  
Fallopia Japonica ◽  
Rpe Cells ◽  
Expression Levels ◽  
Tnf Α

Abstract BackgroundThe increased global incidence of myopia requires the establishment of therapeutic approaches. Previous studies have suggested that inflammation plays an important role in the development and progression of myopia. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella Vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD) and elucidate the underlying mechanisms. MethodsWe used human retinal pigment epithelial cell to study the molecular mechanisms on how FJE and PVE lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia.ResultsMyopia progression was enhanced upon tumor necrosis factor (TNF)-α or interleukin (IL)-6 administration. Expression levels of IL-6, IL-8, and TNF-α were upregulated in retinal pigment epithelium (RPE) cells treated with IL-6 and TNF-α. FJ extract (FJE) + PV extract (PVE) reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-β1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type Ⅰ collagen expression. ConclusionOverall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

scholarly journals Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Peng-Tai Tien ◽  
Chia-Hung Lin ◽  
Chih-Sheng Chen ◽  
Ching-Yao Chang ◽  
Hsiangyu Ku ◽  
...  
Keyword(s):  
Refractive Error ◽  
Transforming Growth Factor Beta ◽  
Axial Length ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Retinal Pigment Epithelial Cell ◽  
Retinal Pigment ◽  
Type I ◽  
Myopia Progression ◽  
Tgf Β1

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: − 0.91 ± 0.023 , atropine: − 0.3 ± 0.08 , and diacerein: − 0.27 ± 0.07   D ) and axial length (control: 0.401 ± 0.017 , atropine: 0.326 ± 0.017 , and diacerein: 0.334 ± 0.016   mm ) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) β1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-β1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

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.

LncRNA HOTAIR promotes endometrial fibrosis by activating TGF-β1/Smad pathway

2020 ◽  
Vol 52 (12) ◽  
pp. 1337-1347
Author(s):  
Jianhong Wu ◽  
Lingge Jin ◽  
Yudi Zhang ◽  
Aihong Duan ◽  
Juhong Liu ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Quantitative Polymerase Chain Reaction ◽  
Endometrial Stromal Cells ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Abstract Homeobox transcript antisense RNA (HOTAIR) is a long non-coding RNA associated with a number of fibrosis-related diseases. The aim of this study was to investigate the specific role of HOTAIR in the development of endometrial fibrosis and to identify the molecular mechanisms underlying this process. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of HOTAIR in samples of intrauterine adhesion (IUA) tissue and in endometrial stromal cells (ESCs) that had been treated with transforming growth factor beta 1 (TGF-β1). Additionally, we transfected ESCs with either overexpression plasmid (pcDNA-HOTAIR) or silencing construct (si-HOTAIR) and then treated these cells with TGF-β1. We then performed RT-qPCR and western blot analysis, along with cell proliferation and apoptosis assays, to investigate the effects of HOTAIR on the transdifferentiation of ESCs into myofibroblasts. The results showed that the expression levels of HOTAIR were significantly elevated in IUA tissue and in ESCs that had been treated with TGF-β1. The overexpression of HOTAIR had a pro-fibrotic effect on ESCs, while the silencing of HOTAIR exerted an anti-fibrotic effect. Most importantly, the protein expression levels of p-Smad2 and p-Smad3 were significantly upregulated in TGF-β1-treated ESCs transfected with pcDNA-HOTAIR and were downregulated after transfection with si-HOTAIR constructs. These data indicate that HOTAIR promotes endometrial fibrosis by activating the TGF-β1/Smad signaling pathway, suggesting that the inhibition of HOTAIR may represent a promising therapeutic option for suppressing endometrial fibrosis.

scholarly journals EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

2020 ◽  
Vol 21 (12) ◽  
pp. 4271 ◽  
Author(s):  
Daisy Y. Shu ◽  
Erik Butcher ◽  
Magali Saint-Geniez
Keyword(s):  
Macular Degeneration ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Retinal Pigment ◽  
Mesenchymal Cells ◽  
Age Related Macular Degeneration ◽  
Mesenchymal Transition ◽  
Age Related

Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

scholarly journals Effects of Lycium barbarum polysaccharide on the photoinduced autophagy of retinal pigment epithelium cells

2022 ◽  
Vol 15 (1) ◽  
pp. 23-30
Author(s):  
Yuan-Yuan Gao ◽  
◽  
Jie Huang ◽  
Wu-Jun Li ◽  
Yang Yu ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Counting ◽  
High Dose ◽  
Lycium Barbarum ◽  
Rpe Cells ◽  
Expression Levels ◽  
Lycium Barbarum Polysaccharide

AIM: To investigate the relationship between autophagy and apoptosis in photoinduced injuries in retinal pigment epithelium (RPE) cells and how Lycium barbarum polysaccharide (LBP) contributes to the increased of RPE cells to photoinduced autophagy. METHODS: In vitro cultures of human RPE strains (ARPE-19) were prepared and randomly divided into the blank control, model, low-dose LBP, middle-dose LBP, high-dose LBP, and 3-methyladenine (3MA) groups. The viability of the RPE cells and apoptosis levels in each group were tested through cell counting kit-8 (CCK8) method with a flow cytometer (Annexin V/PI double staining technique). The expression levels of LC3II, LC3I, and P62 proteins were detected with the immunofluorescence method. The expression levels of beclin1, LC3, P62, PI3K, P-mTOR, mTOR, P-Akt, and Akt proteins were tested through Western blot. RESULTS: LBP considerably strengthens cell viability and inhibits the apoptosis of RPE cells after photoinduction. The PI3K/Akt/mTOR signal pathway is activated because of the upregulation of the phosphorylation levels of Akt and mTOR proteins, and thus autophagy is inhibited. CONCLUSION: LBP can inhibit the excessive autophagy in RPE cells by activating the PI3K/Akt/mTOR signaling pathways and thereby protect RPE cells from photoinduced injuries.

scholarly journals Tangeretin Inhibition of High-Glucose-Induced IL-1β, IL-6, TGF-β1, and VEGF Expression in Human RPE Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Dong Qin ◽  
Yan-rong Jiang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Retinal Pigment ◽  
Antioxidant Properties ◽  
Vegf Expression ◽  
Rpe Cells ◽  
Tgf Β1 ◽  
Human Rpe Cells

Tangeretin, a natural compound extracted from citrus plants, has been reported to have antiproliferative, antidiabetic, anti-invasive, and antioxidant properties. However, the role of tangeretin in diabetic retinopathy (DR) is unknown. In the present study, we investigated whether tangeretin had any effect on the expression of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1), and vascular endothelial growth factor (VEGF) in human retinal pigment epithelial (RPE) cells under high-glucose (HG) conditions. Our results illustrated that HG levels induced IL-1β, IL-6, TGF-β1, and VEGF expression and that tangeretin significantly reduced HG-induced IL-1β, IL-6, TGF-β1, and VEGF expression in human RPE cells. Moreover, tangeretin efficiently inhibited the activation of the protein kinase B (Akt) signalling pathway in HG-stimulated RPE cells. Therefore, tangeretin may serve a role in the treatment of DR.

scholarly journals The RhoA Activator GEF-H1/Lfc Is a Transforming Growth Factor-β Target Gene and Effector That Regulates α-Smooth Muscle Actin Expression and Cell Migration

2010 ◽  
Vol 21 (6) ◽  
pp. 860-870 ◽  
Author(s):  
Anna Tsapara ◽  
Phillip Luthert ◽  
John Greenwood ◽  
Caroline S. Hill ◽  
Karl Matter ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Muscle Actin ◽  
Rpe Cells ◽  
A Genome

Maintenance of the epithelial phenotype is crucial for tissue homeostasis. In the retina, dedifferentiation and loss of integrity of the retinal pigment epithelium (RPE) leads to retinal dysfunction and fibrosis. Transforming growth factor (TGF)-β critically contributes to RPE dedifferentiation and induces various responses, including increased Rho signaling, up-regulation of α-smooth muscle actin (SMA), and cell migration and dedifferentiation. Cellular TGF-β responses are stimulated by different signal transduction pathways: some are Smad dependent and others Smad independent. Alterations in Rho signaling are crucial to both types of TGF-β signaling, but how TGF-β-stimulates Rho signaling is poorly understood. Here, we show that primary RPE cells up-regulated GEF-H1 in response to TGF-β. GEF-H1 was the only detectable Rho exchange factor increased by TGF-β1 in a genome-wide expression analysis. GEF-H1 induction was Smad4-dependant and led to Rho activation. GEF-H1 inhibition counteracted α-SMA up-regulation and cell migration. In patients with retinal detachments and fibrosis, migratory RPE cells exhibited increased GEF-H1 expression, indicating that induction occurs in diseased RPE in vivo. Our data indicate that GEF-H1 is a target and functional effector of TGF-β by orchestrating Rho signaling to regulate gene expression and cell migration, suggesting that it represents a new marker and possible therapeutic target for degenerative and fibrotic diseases.

scholarly journals PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jia He ◽  
Chongde Long ◽  
Zixin Huang ◽  
Xin Zhou ◽  
Xielan Kuang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Induced Apoptosis

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α(one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

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