Base de dados : MEDLINE
Pesquisa : A08.637.300 [Categoria DeCS]
Referências encontradas : 466 [refinar]
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[PMID]:29287085
[Au] Autor:Liu L; Steinle JJ
[Ad] Endereço:Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States of America.
[Ti] Título:Loss of TLR4 in mouse Müller cells inhibits both MyD88-dependent and -independent signaling.
[So] Source:PLoS One;12(12):e0190253, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Müller cells are key to metabolic and ionic regulation in the retina. They also produce a number of inflammatory mediators and are significantly affected in diabetic retinopathy. To investigate the role of toll-like receptor 4 (TLR4) in retinal Müller cells, we crossed TLR4 floxed with PDGFRα-Cre mice to eliminate TLR4 in retinal Müller cells. We performed Western blotting and ELISA analyses to determine whether loss of TLR4 affected myeloid differentiation primary response protein (MyD88)-dependent or -independent signaling, leading to reduced levels of tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL1ß) in whole retinal lysates from the TLR4 floxed and TLR4-PDGFRα-Cre mice. Data show that TLR4-PDGFRα-Cre mice have reduced levels of both the MyD88-dependent and -independent signaling pathways. These studies confirm successful development of a Müller cell-specific TLR4 knockout mouse colony. These mice have reduced MyD88-dependent and -independent signaling pathway proteins, as well as reduced TNFα and IL1ß levels. These mice can be used to dissect TLR4 signaling in disorders affecting retinal Müller cells.
[Mh] Termos MeSH primário: Células Ependimogliais/metabolismo
Fator 88 de Diferenciação Mieloide/metabolismo
Transdução de Sinais
Receptor 4 Toll-Like/fisiologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Ensaio de Imunoadsorção Enzimática
Interleucina-1beta/metabolismo
Camundongos
Camundongos Transgênicos
Receptor 4 Toll-Like/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Interleukin-1beta); 0 (Myd88 protein, mouse); 0 (Myeloid Differentiation Factor 88); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 0 (Tumor Necrosis Factor-alpha)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190253


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[PMID]:28460049
[Au] Autor:Hassan I; Luo Q; Majumdar S; Dominguez JM; Busik JV; Bhatwadekar AD
[Ad] Endereço:Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States.
[Ti] Título:Tumor Necrosis Factor Alpha (TNF-α) Disrupts Kir4.1 Channel Expression Resulting in Müller Cell Dysfunction in the Retina.
[So] Source:Invest Ophthalmol Vis Sci;58(5):2473-2482, 2017 05 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Diabetic patients often are affected by vision problems. We previously identified diabetic retinopathy (DR) as a disease of clock gene dysregulation. TNF-α, a proinflammatory cytokine, is known to be elevated in DR. Müller cells maintain retinal water homeostasis and K+ concentration via Kir4.1 channels. Notably, Kir4.1 expression is reduced in diabetes; however, the interplay of TNF-α, Kir4.1, and clock genes in Müller cells remains unknown. We hypothesize that the Kir4.1 in Müller cells is under clock regulation, and increase in TNF-α is detrimental to Kir4.1. Methods: Long-Evans rats were made diabetic using streptozotocin (STZ). Retinal Kir4.1 expression was determined at different time intervals. Rat Müller (rMC-1) cells were transfected with siRNA for Per2 or Bmal1 and in parallel treated with TNF-α (5-5000 pM) to determine Kir4.1 expression. Results: Kir4.1 expression exhibited a diurnal rhythm in the retina; however, with STZ-induced diabetes, Kir4.1 was reduced overall. Kir4.1 rhythm was maintained in vitro in clock synchronized rMC-1 cells. Clock gene siRNA-treated rMC-1 exhibited a decrease in Kir4.1 expression. TNF-α treatment of rMCs lead to a profound decrease in Kir4.1 due to reduced colocalization of Kir4.1 channels with synapse-associated protein (SAP97) and disorganization of the actin cytoskeleton. Conclusions: Our findings demonstrate that Kir4.1 channels possess a diurnal rhythm, and this rhythm is dampened with diabetes, thereby suggesting that the increase in TNF-α is detrimental to normal Kir4.1 rhythm and expression.
[Mh] Termos MeSH primário: Diabetes Mellitus Experimental
Retinopatia Diabética/genética
Células Ependimogliais/metabolismo
Regulação da Expressão Gênica
Canais de Potássio Corretores do Fluxo de Internalização/genética
RNA Mensageiro/genética
Fator de Necrose Tumoral alfa/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Western Blotting
Células Cultivadas
Ritmo Circadiano
Retinopatia Diabética/tratamento farmacológico
Retinopatia Diabética/metabolismo
Células Ependimogliais/efeitos dos fármacos
Células Ependimogliais/patologia
Imuno-Histoquímica
Canais de Potássio Corretores do Fluxo de Internalização/biossíntese
Ratos
Ratos Long-Evans
Reação em Cadeia da Polimerase em Tempo Real
Retina/efeitos dos fármacos
Retina/metabolismo
Retina/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Kcnj10 (channel)); 0 (Potassium Channels, Inwardly Rectifying); 0 (RNA, Messenger); 0 (Tumor Necrosis Factor-alpha)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180124
[Lr] Data última revisão:
180124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-20712


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[PMID]:29186716
[Au] Autor:Eichler W; Savkovic-Cvijic H; Bürger S; Beck M; Schmidt M; Wiedemann P; Reichenbach A; Unterlauft JD
[Ad] Endereço:Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany.
[Ti] Título:Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation.
[So] Source:Cell Physiol Biochem;44(4):1411-1424, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. METHODS: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. RESULTS: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. CONCLUSIONS: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases.
[Mh] Termos MeSH primário: Células Ependimogliais/metabolismo
Proteínas do Olho/metabolismo
Fatores de Crescimento Neural/metabolismo
Fator de Transcrição STAT3/metabolismo
Serpinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Hipóxia Celular
Sobrevivência Celular/efeitos dos fármacos
Técnicas de Cocultura
Óxidos S-Cíclicos/farmacologia
Células Ependimogliais/citologia
Proteínas do Olho/antagonistas & inibidores
Proteínas do Olho/genética
Proteínas do Olho/farmacologia
Interleucina-6/farmacologia
Lipase/antagonistas & inibidores
Lipase/genética
Lipase/metabolismo
Camundongos
Fatores de Crescimento Neural/antagonistas & inibidores
Fatores de Crescimento Neural/genética
Fatores de Crescimento Neural/farmacologia
Fosforilação/efeitos dos fármacos
Interferência de RNA
RNA Interferente Pequeno/metabolismo
Ratos
Receptores de Neuropeptídeos/metabolismo
Células Ganglionares da Retina/metabolismo
Fator de Transcrição STAT3/antagonistas & inibidores
Serpinas/genética
Serpinas/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic S-Oxides); 0 (Eye Proteins); 0 (Interleukin-6); 0 (Nerve Growth Factors); 0 (RNA, Small Interfering); 0 (Receptors, Neuropeptide); 0 (STAT3 Transcription Factor); 0 (Serpins); 0 (pigment epithelium-derived factor); 0 (pigment epithelium-derived factor receptor); 0 (stattic); EC 3.1.1.3 (Lipase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1159/000485537


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[PMID]:29111459
[Au] Autor:Chen H; Song Z; Ying S; Yang X; Wu W; Tan Q; Ju X; Wu W; Zhang X; Qu J; Wang Y
[Ad] Endereço:Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
[Ti] Título:Myeloid differentiation protein 2 induced retinal ischemia reperfusion injury via upregulation of ROS through a TLR4-NOX4 pathway.
[So] Source:Toxicol Lett;282:109-120, 2018 Jan 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Retinal ischemia reperfusion (I/R) injury is common in many ophthalmic diseases. Recent studies have shown that toll-like receptor 4 (TLR4) is involved in ischemic retinal injury. Activation of TLRs requires specific accessory proteins such as myeloid differentiation protein 2 (MD2), which facilitate in ligand responsiveness. Therefore, inhibiting MD2 may be a novel approach to modulate TLR4 signaling and deleterious downstream effects in ischemic retinal injury. We used human Müller MIO-M1 cells treated with tert-butyl hydroperoxide (TBHP) to establish an in vitro I/R model of oxidative injury and tested the therapeutic effect of inhibiting MD2. Furthermore, we inhibited MD2 in a mouse model of retinal I/R injury and confirmed the results using MD2 knockout mice. Our studies show that pharmacological inhibition of MD2 prevented TBHP-induced reactive oxygen species (ROS) generation, inflammation and subsequent apoptosis in Müller cells. We also show that retinal I/R injury in mice induced functional deficits, increased ROS levels, inflammation and apoptosis. These pathological changes were not observed in MD2 knockout mice and attenuated when MD2 was inhibited in wildtype mice. In addition, we discovered that the mechanism of these therapeutic effects involved regulation of NADPH oxidase 4 (NOX4)-MD2-TLR4 complex formation. This study provides evidence that MD2 plays a key role in the pathogenesis of retinal I/R damage by participating in TLR4-NOX4 complex formation and elaboration of oxidative and inflammatory damage. Hence, inhibition of MD2 may reduce TLR-dependent damage during retinal I/R injury.
[Mh] Termos MeSH primário: Antígeno 96 de Linfócito/antagonistas & inibidores
NADPH Oxidase 4/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Traumatismo por Reperfusão/metabolismo
Doenças Retinianas/metabolismo
Receptor 4 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Chalconas/farmacologia
Modelos Animais de Doenças
Células Ependimogliais
Seres Humanos
Antígeno 96 de Linfócito/genética
Camundongos Endogâmicos C57BL
Camundongos Knockout
Estresse Oxidativo/efeitos dos fármacos
Transdução de Sinais
terc-Butil Hidroperóxido/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(3,4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one); 0 (Chalcones); 0 (Ly96 protein, mouse); 0 (Lymphocyte Antigen 96); 0 (Reactive Oxygen Species); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 955VYL842B (tert-Butylhydroperoxide); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (Nox4 protein, mouse)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171108
[St] Status:MEDLINE


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[PMID]:28980000
[Au] Autor:Hu P; Hunt NH; Arfuso F; Shaw LC; Uddin MN; Zhu M; Devasahayam R; Adamson SJ; Benson VL; Chan-Ling T; Grant MB
[Ad] Endereço:Department of Anatomy, Bosch Institute, University of Sydney, New South Wales, Australia.
[Ti] Título:Increased Indoleamine 2,3-Dioxygenase and Quinolinic Acid Expression in Microglia and Müller Cells of Diabetic Human and Rodent Retina.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5043-5055, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels). Results: Based on morphologic criteria, CD39+/ionized calcium binding adaptor molecule 1(Iba-1+) resident microglia and CD39-/Iba-1+ bone marrow-derived macrophages were present at higher density in T1D (13% increase) and T2D (26% increase) human retinas when compared with controls. The density and brightness of IDO+ microglia were increased in both T1D and T2D human retinas. The intensity of QUIN+ expression on CD39+ microglia and VIM+ Müller cells was greatly increased in both human T1D and T2D retinas. T1D retinas showed a 63% loss of NeuN+ neurons and T2D retinas lost approximately 43% when compared with nondiabetic human retinas. Few QUIN+ microglia-like cells were seen in nondiabetic retinas, but the numbers increased 18-fold in T1D and 7-fold in T2D in the central retina. In T1D rat retinas, the density of IDO+ microglia increased 2.8-fold and brightness increased 2.1-fold when compared with controls. Conclusions: Our findings suggest that IDO and QUIN expression in the retinas of diabetic rats and humans could contribute to the neuronal degeneration that is characteristic of diabetic retinopathy.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Retinopatia Diabética/metabolismo
Células Ependimogliais/metabolismo
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Microglia/metabolismo
Ácido Quinolínico/metabolismo
Retina/metabolismo
[Mh] Termos MeSH secundário: Idoso
Animais
Antígenos CD/metabolismo
Antígenos Nucleares/metabolismo
Apirase/metabolismo
Proteínas de Ligação ao Cálcio/metabolismo
Proteínas de Ligação a DNA/metabolismo
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Tipo 1/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Retinopatia Diabética/patologia
Células Ependimogliais/patologia
Feminino
Técnica Indireta de Fluorescência para Anticorpo
Seres Humanos
Masculino
Proteínas dos Microfilamentos/metabolismo
Microglia/patologia
Microscopia Confocal
Meia-Idade
Proteínas do Tecido Nervoso/metabolismo
Ratos
Ratos Sprague-Dawley
Retina/patologia
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIF1 protein, human); 0 (Aif1 protein, rat); 0 (Antigens, CD); 0 (Antigens, Nuclear); 0 (Biomarkers); 0 (Calcium-Binding Proteins); 0 (DNA-Binding Proteins); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Microfilament Proteins); 0 (Nerve Tissue Proteins); 0 (NeuN protein, rat); 0 (Vimentin); 0 (neuronal nuclear antigen NeuN, human); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); F6F0HK1URN (Quinolinic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21654


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[PMID]:28973331
[Au] Autor:Shiode Y; Morizane Y; Matoba R; Hirano M; Doi S; Toshima S; Takahashi K; Araki R; Kanzaki Y; Hosogi M; Yonezawa T; Yoshida A; Shiraga F
[Ad] Endereço:Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
[Ti] Título:The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure.
[So] Source:Invest Ophthalmol Vis Sci;58(11):4847-4855, 2017 Sep 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To investigate the mechanism of macular hole (MH) closure following the inverted internal limiting membrane (ILM) technique. Methods: We performed the inverted ILM flap surgical technique as an experimental MH model in monkeys, and investigated the process of MH closure immunohistochemically. We then investigated the effects of type IV collagen, fibronectin, and laminin, which are constituent proteins of the ILM, on the proliferation and migration of cultivated Müller cells (MIO-M1). We also investigated the expression of neurotrophic factors and basic fibroblast growth factor (bFGF) in human ILM and MIO-M1 cells, and the effect of MIO-M1 migration on the expression of these factors, via immunohistochemical staining and the real-time reverse transcription polymerase chain reaction. Results: Ten days after inverted ILM flap surgery, the MH had closed and proliferating glial fibrillary acidic protein (GFAP)-positive cells surrounded the ILM. Type IV collagen, fibronectin, and laminin all enhanced the proliferation of MIO-M1 cells, and type IV collagen and fibronectin enhanced the migration of MIO-M1 cells. Neurotrophic factors and bFGF were present on the surface of the human ILM, and MIO-M1 cells produced these factors. Neurotrophic factors and bFGF were expressed to a significantly greater extent by migrating MIO-M1 cells than by these cells in their static state. Conclusions: During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.
[Mh] Termos MeSH primário: Membrana Epirretiniana/cirurgia
Perfurações Retinianas/cirurgia
Retalhos Cirúrgicos
Vitrectomia/métodos
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Membrana Basal/cirurgia
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Colágeno Tipo IV/farmacologia
Modelos Animais de Doenças
Células Ependimogliais/efeitos dos fármacos
Células Ependimogliais/metabolismo
Membrana Epirretiniana/metabolismo
Fator 2 de Crescimento de Fibroblastos/metabolismo
Fibronectinas/farmacologia
Laminina/farmacologia
Macaca fascicularis
Masculino
Fatores de Crescimento Neural/metabolismo
Fatores de Crescimento Neural/farmacologia
Perfurações Retinianas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type IV); 0 (Fibronectins); 0 (Laminin); 0 (Nerve Growth Factors); 103107-01-3 (Fibroblast Growth Factor 2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21756


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[PMID]:28917843
[Au] Autor:Farag MI; Yoshikawa Y; Maeta K; Kataoka T
[Ad] Endereço:Division of Molecular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
[Ti] Título:Rapgef2, a guanine nucleotide exchange factor for Rap1 small GTPases, plays a crucial role in adherence junction (AJ) formation in radial glial cells through ERK-mediated upregulation of the AJ-constituent protein expression.
[So] Source:Biochem Biophys Res Commun;493(1):139-145, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap1, characterized by possession of the Ras/Rap-associating domains and implicated in the etiology of schizophrenia. We previously found that dorsal telencephalon-specific Rapgef2 conditional knockout mice exhibits severe defects in formation of apical surface adherence junctions (AJs) and localization of radial glial cells (RGCs). In this study, we analyze the underlying molecular mechanism by using primary cultures of RGCs established from the developing cerebral cortex. The results show that Rapgef2-deficient RGCs exhibit a decreased ability of neurosphere formation, morphological changes represented by regression of radial glial (RG) fibers and reduced expression of AJ-constituent proteins such as N-cadherin, zonula occludens-1, E-cadherin and ß-catenin. Moreover, siRNA-mediated knockdown of Rapgef2 or Rap1A inhibits the AJ protein expression and RG fiber formation while overexpression of Rapgef2, Rapgef6, Rap1A or Rap1B in Rapgef2-deficient RGCs restores them. Furthermore, Rapgef2-deficient RGCs exhibit a reduction in phosphorylation of extracellular signal-regulated kinase (ERK) leading to downregulation of the expression of c-jun, which is implicated in the AJ protein expression. These results indicate a crucial role of the Rapgef2-Rap1A-ERK-c-jun pathway in regulation of the AJ formation in RGCs.
[Mh] Termos MeSH primário: Junções Aderentes/fisiologia
Junções Aderentes/ultraestrutura
Células Ependimogliais/metabolismo
Células Ependimogliais/ultraestrutura
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Fatores de Troca do Nucleotídeo Guanina/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Sistema de Sinalização das MAP Quinases/fisiologia
Camundongos
Camundongos Knockout
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CNrasGEF protein, mouse); 0 (Guanine Nucleotide Exchange Factors); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170918
[St] Status:MEDLINE


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[PMID]:28886036
[Au] Autor:Ishida T; Yoshida T; Shinohara K; Cao K; Nakahama KI; Morita I; Ohno-Matsui K
[Ad] Endereço:Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
[Ti] Título:Potential role of sirtuin 1 in Müller glial cells in mice choroidal neovascularization.
[So] Source:PLoS One;12(9):e0183775, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study investigated the potential role of sirtuin 1 in Müller glial cells in choroidal neovascularization. In the in vitro study, primary Müller glial cells were cultured and treated with resveratrol, a sirtuin 1 activator. Glial fibrillary acidic protein expression and angiogenesis-related gene expression were examined using quantitative polymerase chain reaction and phagocytosis, as a marker of Müller glial cell function; in addition, a latex bead assay was used to analyze cell function. For the in vivo study, choroidal neovascularization was induced in C57BL/6 mice via laser photocoagulation, and resveratrol was administered intravitreally. Eyecup whole mounts were created to measure choroidal neovascularization volumes on day 7. Immunohistochemical analysis with anti-glial fibrillary acidic protein antibody was used to detect Müller glial cell activation in eyes with choroidal neovascularization on day 1, 3, 5, and 7 after laser surgery. Resveratrol significantly promoted glial fibrillary acidic protein, anti-angiogenic factor, pigment epithelium-derived factor, and thrombospondin-1 expression in the cells as well as the phagocytic activities. Treatment of the choroidal neovascularization model with resveratrol resulted in early activation of Müller glial cells near choroidal neovascularization sites. Resveratrol-activated cells but not the controls migrated to the top of choroidal neovascularization sites and into the lesions from day 3. Resveratrol reduced the choroidal neovascularization size relative to controls. In conclusion, sirtuin 1 activation in Müller glial cells suppressed the development of choroidal neovascularization, and therefore, might be a therapeutic option.
[Mh] Termos MeSH primário: Células Ependimogliais/metabolismo
Sirtuína 1/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas do Olho/metabolismo
Proteína Glial Fibrilar Ácida/metabolismo
Imuno-Histoquímica
Camundongos
Camundongos Endogâmicos C57BL
Fatores de Crescimento Neural/metabolismo
Neuroglia/metabolismo
Serpinas/metabolismo
Trombospondina 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eye Proteins); 0 (Glial Fibrillary Acidic Protein); 0 (Nerve Growth Factors); 0 (Serpins); 0 (Thrombospondin 1); 0 (pigment epithelium-derived factor); 0 (thrombospondin-1, mouse); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183775


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[PMID]:28846772
[Au] Autor:Baumann B; Sterling J; Song Y; Song D; Fruttiger M; Gillies M; Shen W; Dunaief JL
[Ad] Endereço:F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States.
[Ti] Título:Conditional Müller Cell Ablation Leads to Retinal Iron Accumulation.
[So] Source:Invest Ophthalmol Vis Sci;58(10):4223-4234, 2017 Aug 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Retinal iron accumulation is observed in a wide range of retinal degenerative diseases, including AMD. Previous work suggests that Müller glial cells may be important mediators of retinal iron transport, distribution, and regulation. A transgenic model of Müller cell loss recently demonstrated that primary Müller cell ablation leads to blood-retinal barrier leakage and photoreceptor degeneration, and it recapitulates clinical features observed in macular telangiectasia type 2 (MacTel2), a rare human disease that features Müller cell loss. We used this mouse model to determine the effect of Müller cell loss on retinal iron homeostasis. Methods: Changes in total retinal iron levels after Müller cell ablation were measured using inductively coupled plasma mass spectrometry. Corresponding changes in the expression of iron flux and iron storage proteins were determined using quantitative PCR, Western analysis, and immunohistochemistry. Results: Müller cell loss led to blood-retinal barrier breakdown and increased iron levels throughout the neurosensory retina. There were corresponding changes in mRNA and/or protein levels of ferritin, transferrin receptor, ferroportin, Zip8, and Zip14. There were also increased iron levels within the RPE of retinal sections from a patient with MacTel2 and both RPE and neurosensory retina of a patient with diabetic retinopathy, which, like MacTel2, causes retinal vascular leakage. Conclusion: This study shows that Müller cells and the blood-retinal barrier play pivotal roles in the regulation of retinal iron homeostasis. The retinal iron accumulation resulting from blood-retinal barrier dysfunction may contribute to retinal degeneration in this model and in diseases such as MacTel2 and diabetic retinopathy.
[Mh] Termos MeSH primário: Modelos Animais de Doenças
Células Ependimogliais/patologia
Ferro/metabolismo
Retina/metabolismo
Telangiectasia Retiniana/metabolismo
[Mh] Termos MeSH secundário: Idoso
Animais
Barreira Hematorretiniana/metabolismo
Barreira Hematorretiniana/patologia
Western Blotting
Permeabilidade Capilar
Proteínas de Transporte de Cátions/genética
Proteínas de Transporte de Cátions/metabolismo
Feminino
Ferritinas/genética
Ferritinas/metabolismo
Seres Humanos
Imuno-Histoquímica
Masculino
Espectrometria de Massas
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Camundongos Transgênicos
Meia-Idade
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Receptores da Transferrina/genética
Receptores da Transferrina/metabolismo
Telangiectasia Retiniana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cation Transport Proteins); 0 (RNA, Messenger); 0 (Receptors, Transferrin); 0 (SLC39A14 protein, mouse); 0 (Slc39a8 protein, mouse); 0 (metal transporting protein 1); 9007-73-2 (Ferritins); E1UOL152H7 (Iron)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21743


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[PMID]:28818394
[Au] Autor:Tsukahara R; Umazume K; McDonald K; Kaplan HJ; Tamiya S
[Ad] Endereço:Department of Ophthalmology and Visual Sciences, University of Louisville, 301 E Muhammad Ali Blvd., Louisville, KY 40202, USA; Department of Ophthalmology, Tokyo Medical University, Ibaraki Medical Center, 3-20-1 Chuo, Ami, Inashiki-gun, Ibaraki 300-0332, Japan.
[Ti] Título:Focal adhesion kinase family is involved in matrix contraction by transdifferentiated Müller cells.
[So] Source:Exp Eye Res;164:90-94, 2017 Nov.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transdifferentiated Müller cells that adopt a fibroblastic/myofibroblastic phenotype have been identified in epiretinal membranes (ERMs) in several ocular disorders, and have been implicated to play a role in the formation and/or the contraction of ERMs. We have previously demonstrated that dasatinib, a dual inhibitor of Src-family kinases and Abl kinase, can prevent matrix contraction by transdifferentiated Müller cells. In this study, we examined molecules involved in matrix contraction downstream of primary dasatinib targets. Tyrosine phosphorylation of focal adhesion kinase (FAK) family members FAK and PYK2 was significantly reduced by dasatinib, and select inhibitors for these kinases PF431396, which inhibits both FAK and PYK2, and PF573228, which only inhibits FAK and not PYK2, significantly reduced matrix contraction by transdifferentiated Müller cells. Dasatinib and PF431396 significantly reduced phosphorylation of Hic-5, a protein implicated to play a role in focal adhesions and cell signaling. Our data shows that FAK family members are involved in matrix contraction by transdifferentiated Müller cells, and also implicates that Hic-5 is situated downstream of the FAK family within the signaling pathway.
[Mh] Termos MeSH primário: Dasatinibe/farmacologia
Células Ependimogliais/efeitos dos fármacos
Matriz Extracelular/efeitos dos fármacos
Proteína-Tirosina Quinases de Adesão Focal/fisiologia
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Transdiferenciação Celular
Células Ependimogliais/metabolismo
Matriz Extracelular/metabolismo
Quinase 1 de Adesão Focal/metabolismo
Quinase 2 de Adesão Focal/metabolismo
Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); EC 2.7.10.2 (Focal Adhesion Kinase 1); EC 2.7.10.2 (Focal Adhesion Kinase 2); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); RBZ1571X5H (Dasatinib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE



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