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Molecules, Vol. 28, Pages 2236: Lipopolysaccharide Activating NF-kB Signaling by Regulates HTRA1 Expression in Human Retinal Pigment Epithelial Cells
glin Yang Inflammation and elevated expression of high temperature requirement A serine peptidase 1 (HTRA1) are known high risk factors for age-related macular degeneration (AMD). However, the specific mechanism that HTRA1 causes AMD and the relationship between HTRA1 and inflammation remains unclear. We found that lipopolysaccharide (LPS) induced inflammation enhanced the expression of HTRA1, NF-κB, and p-p65 in ARPE-19 cells. Overexpression of HTRA1 up-regulated NF-κB expression, and on the other hand knockdown of HTRA1 down-regulated the expression of NF-κB. Moreover, NF-&am...
Source: Molecules - February 28, 2023 Category: Chemistry Authors: Shengliu Pan Min Liu Huijuan Xu Junlan Chuan Zhenglin Yang Tags: Article Source Type: research

Rubicon regulates A2E-induced autophagy impairment in the retinal pigment epithelium implicated in the pathology of age-related macular degeneration
Biochem Biophys Res Commun. 2021 Mar 16;551:148-154. doi: 10.1016/j.bbrc.2021.02.148. Online ahead of print.ABSTRACTWaste product deposition and light stress in the retinal pigment epithelium (RPE) are crucial factors in the pathogenesis of various retinal degenerative diseases, including age-related macular degeneration (AMD), a leading cause of vision loss in elderly individuals worldwide. Given that autophagy in the RPE suppresses waste accumulation, determining the molecular mechanism by which autophagy is compromised in degeneration is necessary. Using polarized human RPE sheets, we found that bis-retinoid N-retinyl-N...
Source: Biochemical and Biophysical Research communications - March 19, 2021 Category: Biochemistry Authors: Satoru Ando Noriyasu Hashida Daisuke Yamashita Tsuyoshi Kawabata Kazunobu Asao Satoshi Kawasaki Kazushi Sakurai Tamotsu Yoshimori Kohji Nishida Source Type: research

RNA therapeutics in ophthalmology - translation to clinical trials.
Abstract The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the effic...
Source: Experimental Eye Research - February 3, 2021 Category: Opthalmology Authors: Gupta A, Kafetzis KN, Tagalakis AD, Yu-Wai-Man C Tags: Exp Eye Res Source Type: research

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

Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration
Deposition of hydroxyapatite (HAP) basal to the retinal pigment epithelium (RPE) is linked to the progression of age-related macular degeneration (AMD). Serum-deprivation of RPE cells in culture mimics some features of AMD. We now show that serum-deprivation also leads to the induction of amelotin (AMTN), a protein involved in hydroxyapatite mineralization in enamel. HAP is formed in our culture model and is blocked by siRNA inhibition of AMTN expression. In situ hybridization and immunofluorescence imaging of human eye tissue show that AMTN is expressed in RPE of donor eyes with geographic atrophy ( “dry” AMD) in regi...
Source: Translational Research - February 25, 2020 Category: Research Authors: Dinusha Rajapakse, Katherine Peterson, Sanghamitra Mishra, Jianguo Fan, Joshua Lerner, Maria Campos, Graeme Wistow Source Type: research

Intravitreal Ets1 siRNA alleviates choroidal neovascularization in a mouse model of age-related macular degeneration
In this study, Ets1 increased and localized in the macrophages and microglia of a mouse laser-induced CNV region. Ets1 siRNA intravitreal injection ameliorated the leakage and area of CNV, as well as inhibiting the dysfunction of retinal pigment epithelium (RPE) cells and the activation of macrophages/microglia. Taken together, we provide a new insight into the molecular mechanism of CNV progression, in which Ets1 can be a new therapeutic target.
Source: Cell and Tissue Research - February 28, 2019 Category: Cytology Source Type: research

Up-regulation of P-gp via NF- κB activation confers protection against oxidative damage in the retinal pigment epithelium cells.
In conclusion, P-gp can provide moderate cytoprotection for the human RPE cells by ameliorating the mitochondrial dysfunction and NF-κB activation may be a potential regulator of P-gp expression response to oxidative stress. PMID: 30496729 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - November 26, 2018 Category: Opthalmology Authors: Feng Q, Yang W, Gao Z, Ruan X, Zhang Y Tags: Exp Eye Res Source Type: research

Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1 α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (Müller) cells
ConclusionDEC2 could upregulate retinalVEGF gene expression through modulation of HIF1 α levels under hypoxic conditions.
Source: Japanese Journal of Ophthalmology - September 24, 2018 Category: Opthalmology Source Type: research

Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival
In conclusion, we clarified the relationship between acceleration of the autophagy pathway and the cytoprotective effects of Nrf2 activation in RPE cells and zebrafish retina. These findings indicated that Nrf2 activation could be a promising therapeutic approach for non-exudative AMD by supporting RPE maintenance.Graphical abstract
Source: Redox Biology - September 5, 2018 Category: Biology 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