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Osmotic regulation of aquaporin-8 expression in retinal pigment epithelial cells in vitro: Dependence on KATP channel activation.
Conclusions: The data indicate that hyperosmotic expression of AQP8 in RPE cells is dependent on the activation of KATP channels. The data suggest that AQP8 activity decreases the hypoxic VEGF expression and improves the viability of RPE cells which may have impact for ischemic retinal diseases like diabetic retinopathy and age-related macular degeneration. PMID: 33456300 [PubMed - in process]
Source: Molecular Vision - January 20, 2021 Category: Molecular Biology Tags: Mol Vis Source Type: research

Gremlin-1: An endogenous BMP antagonist induces epithelial-mesenchymal transition and interferes with redifferentiation in fetal RPE cells with repeated wounds.
Conclusions: In fetal RPE cells, Gremlin-1 induces EMT and inhibits redifferentiation by promoting the TGF-β pathway and inhibiting the BMP pathway. GREM1 silencing alleviates EMT and increases the redifferentiation of cells by relieving the blockade of the BMP pathway. However, GREM1 silencing has no effects on the TGF-β pathway. Thus, Gremlin-1 may serve as a novel target to treat proliferative vitreoretinopathy (PVR) and inhibit subretinal fibrosis, which is a risk factor for influencing the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) on neovascular age-related macular degeneration (nAMD...
Source: Molecular Vision - November 10, 2019 Category: Molecular Biology Tags: Mol Vis Source Type: research

Activator protein-1 contributes to the NaCl-induced expression of VEGF and PlGF in RPE cells.
Conclusions: The data indicate that AP-1 is activated in RPE cells in response to extracellular hyperosmolarity and mediates in part via the NaCl-induced expression of VEGF and PlGF, and secretion of PlGF. It is suggested that high consumption of dietary salt may exacerbate the angiogenic response of RPE cells in part via activation of AP-1. PMID: 30310263 [PubMed - in process]
Source: Molecular Vision - October 13, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research

Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation.
Abstract Autophagy and exosome secretion play important roles in a variety of physiological and disease states, including the development of age-related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways of activation. Low oxidative damage in ARPE-19 cells, alters both autophagy and exosome biogenesis. Moreover, oxidative stress modifies the protein and genetic cargo of exosomes, possibly affecting the fate of surrounding cells. In order to understand the connection between these two mechanisms and their impact on angiogenesis, stressed ARPE-19 cells were ...
Source: J Cell Mol Med - August 21, 2018 Category: Molecular Biology Authors: Atienzar-Aroca S, Serrano-Heras G, Freire Valls A, Ruiz de Almodovar C, Muriach M, Barcia JM, Garcia-Verdugo JM, Romero FJ, Sancho-Pelluz J Tags: J Cell Mol Med Source Type: research

Osmotic and hypoxic induction of the complement factor C9 in cultured human retinal pigment epithelial cells: Regulation of VEGF and NLRP3 expression.
Conclusions: The expression of the C9 gene in cultured RPE cells is highly induced by extracellular hyperosmolarity, hypoxia, and oxidative stress. The data may support the assumption that C9 gene expression may stimulate the expression of inflammatory (NLRP3) and angiogenic growth factors (VEGF) in RPE cells. Extracellular C9 protein may attenuate this effect, in part via negative regulation of the C9 mRNA level. PMID: 30090015 [PubMed - in process]
Source: Molecular Vision - August 11, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research

Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation.
Conclusions: This study showed that YAP upregulation promoted CNV formation by upregulating the proliferation of endothelial cells, providing evidence for the molecular mechanisms of CNV and suggesting a novel molecular target for nAMD treatment. PMID: 29422766 [PubMed - in process]
Source: Molecular Vision - February 11, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research

Osmotic induction of placental growth factor in retinal pigment epithelial cells in vitro: contribution of NFAT5 activity.
Abstract One risk factor of neovascular age-related macular degeneration is systemic hypertension; hypertension is mainly caused by extracellular hyperosmolarity after consumption of dietary salt. In retinal pigment epithelial (RPE) cells, high extracellular osmolarity induces vascular endothelial growth factor (VEGF)-A (Hollborn et al. in Mol Vis 21:360-377, 2015). The aim of the present study was to determine whether extracellular hyperosmolarity and chemical hypoxia trigger the expression of further VEGF family members including placental growth factor (PlGF) in human RPE cells. Hyperosmotic media were made up ...
Source: Molecular Biology Reports - May 25, 2016 Category: Molecular Biology Authors: Hollborn M, Reichmuth K, Prager P, Wiedemann P, Bringmann A, Kohen L Tags: Mol Biol Rep Source Type: research

TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.
CONCLUSIONS: Our results support the thinking that TNF-α contributes to CNV by upregulating VEGF production in RPE cells through ROS-dependent activation of β-catenin signaling. These results provide mechanisms of crosstalk between inflammatory mediator, TNF-α, and ROS in RPE cells. PMID: 26900328 [PubMed - in process]
Source: Molecular Vision - February 25, 2016 Category: Molecular Biology Tags: Mol Vis Source Type: research

Mitochondrial DNA has a pro-inflammatory role in AMD
This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD. Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - September 7, 2015 Category: Molecular Biology Source Type: research

Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in retinal pigment epithelial cells: Involvement of NFAT5.
CONCLUSIONS: Hyperosmolarity induces the gene transcription of AQP5, AQP8, and VEGF, as well as the secretion of VEGF from RPE cells. The data suggest that high salt intake resulting in osmotic stress may aggravate neovascular retinal diseases and edema via the stimulation of VEGF production in RPE. The downregulation of AQP5 under hypoxic conditions may prevent the resolution of edema. PMID: 25878490 [PubMed - in process]
Source: Molecular Vision - April 19, 2015 Category: Molecular Biology Tags: Mol Vis Source Type: research

Adeno-associated virus type 8 vector-mediated expression of siRNA targeting vascular endothelial growth factor efficiently inhibits neovascularization in a murine choroidal neovascularization model.
CONCLUSIONS: These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV2/8-mediated siRNA-VEGF expression. In vivo gene therapy may thus be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration. PMID: 24744609 [PubMed - indexed for MEDLINE]
Source: Molecular Vision - November 16, 2014 Category: Molecular Biology Tags: Mol Vis Source Type: research