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1.
Exp Eye Res ; 181: 157-162, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30716329

RESUMEN

To assess the cellular stress evoked by exposure of Brilliant Blue-G (BBG), adult retinal pigment epithelial (ARPE-19) cells were treated with various dilutions of BBG in balanced salt solution plus (BSS-PLUS) with and without endoillumination (Alcon Constellation Vision System). The treatments lasted for acute periods of 2 and 5 min. MTT and presto blue assays were performed to assess the changes in cell viability; reactive oxygen species (ROS) production was quantified by DCFDA (dichlorofluorescin diacetate) assay, and the expression of inflammatory stress and endoplasmic reticulum (ER) genes were quantified by qPCR. We observed no reduction in cell viability at 2 min of dye treatment with and without endoillumination while at 5 min exposure, a reduction in cell viability at all concentrations of the dye was observed compared to control. Though there was an increase in ROS with endoillumination, it was insignificant. There was no change in the mRNA expression of TNF-α while that of GRP78, and inflammatory genes viz. IL-8, IL-1ß showed a significant increase at 0.5 mg/ml dye with endoillumination. BBG reduced cell viability with increasing concentration and time. The undiluted concentration of the dye results in inflammatory stress compared to the diluted formulations. Interestingly, increased GRP78 at undiluted concentration indicates a protective response in cells exposed to light. However, further studies are needed to evaluate the effect of cellular stress on the visual outcome. We infer that the commercially available formulation of BBG is safe for the RPE, at the recommended dose for a short duration however its toxicity to other cell types need to be addressed.


Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Enfermedades de la Retina/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Colorantes de Rosanilina/farmacología , Apoptosis , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Chaperón BiP del Retículo Endoplásmico , Células Epiteliales/metabolismo , Humanos , Indicadores y Reactivos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Enfermedades de la Retina/patología , Epitelio Pigmentado de la Retina/patología , Cirugía Vitreorretiniana
2.
Microvasc Res ; 122: 136-145, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30144414

RESUMEN

Neovascularization in retina and choroid involves interplay of many cytokines and growth factors. Vascular endothelial growth factor (VEGF) being a pro-angiogenic molecule has been found to be high in aqueous and vitreous humour of patients with proliferative diabetic retinopathy (PDR). VEGF is also found in the fibroblast and retinal pigment epithelial cells (RPE) of choroidal neovascular (CNV) membranes isolated from patients. Though anti-VEGF agents cause regression of clinically visible new vessels, there is evidence that they increase the occurrence of retinal tractional detachment and other adverse effects in PDR and CNV treatments. Adiponectin (APN) is a cytokine, found to be involved in the pathobiology of PDR. It is unclear whether APN plays a reparative or pathological role in the disease condition. In this study, we explored the effect of APN on tube formation in the primary culture of human umbilical vein macrovascular endothelial cells (HUVEC), human retinal microvascular endothelial cells (hREC) and human choroidal endothelial cells (hCEC). Anti-VEGF agent, bevacizumab (avastin) was used as a control. Full-length pAc-APN transfected in HUVEC, hRECs and hCECs inhibited basal tube formation and migration comparable to bevacizumab (Avastin™). In hRECs, full length pAc-APN reduced VEGF or PDR vitreous mediated migration. In a similar way, rAPN significantly disrupted VEGF and PDR vitreous induced tube formation in HUVEC and hREC. Moreover, rAPN significantly reduced VEGF influenced proliferation and phosphorylation of ERK1/2 in hREC. Altogether, our study suggests that APN may be effective in the treatment of retinal neovascularization.


Asunto(s)
Adiponectina/farmacología , Inhibidores de la Angiogénesis/farmacología , Coroides/irrigación sanguínea , Células Endoteliales/efectos de los fármacos , Microvasos/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Vasos Retinianos/efectos de los fármacos , Adiponectina/genética , Adiponectina/metabolismo , Inductores de la Angiogénesis/farmacología , Bevacizumab/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Células Endoteliales/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Microvasos/metabolismo , Neovascularización Patológica , Fenotipo , Fosforilación , Vasos Retinianos/metabolismo , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/farmacología , Cuerpo Vítreo/metabolismo
3.
Sci Rep ; 8(1): 10426, 2018 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-29993014

RESUMEN

Angiogenesis is a critical process involved in normal physiology. Pathological angiogenesis is observed in vascular diseases and neoplasia. The propeptide domain of LOX (LOX-PP) has been shown to inhibit tumorigenesis in various cancers. In this study, we explored the role of both overexpressed and recombinant LOX-PP in naïve human umbilical vein endothelial cell with the addition of vascular endothelial growth factor (VEGF). Primarily, we observed a significant reduction in the angiogenesis signaling pathways upon LOX-PP overexpression by proteomic analysis. Further functional analysis showed that the VEGF induced cell proliferation, migration, adhesion and tube formation was inhibited by LOX-PP. Moreover, LOX-PP arrested cells at S-phase, reduced F-actin levels and decreased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK). The anti-angiogenic effect of LOX-PP was further confirmed by the reduction in the vascular network formation in chick chorioallantoic membrane (CAM). These results indicate that inhibition of angiogenesis events is not only achieved by overexpressing LOX-PP but also by addition of rLOX-PP. Taken together our findings discovered the anti-angiogenic role of LOX-PP in endothelial cells which suggests that harnessing this potential can be a promising strategy to inhibit angiogenesis.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Células Endoteliales/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Proteína-Lisina 6-Oxidasa/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Precursores de Proteínas , Proteína-Lisina 6-Oxidasa/uso terapéutico
4.
Microvasc Res ; 117: 37-43, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29307595

RESUMEN

Early growth response-1 (Egr-1) protein upregulation is reported in diabetes and vascular disorders. This study aims at deciphering its role in hyperglycemia induced changes of retinal endothelium. Human retinal endothelial cells (hRECs) were exposed to hyperglycemia (25mM) and normoglycemia (5.5mM). Gene silencing was done using siRNA against Egr-1. Transcript and protein level analysis of Egr-1 and gene targets were done using qPCR and immunoblotting respectively in hRECs, diabetic and nondiabetic human retina and immunofluorescence for localization in retinal sections. Hyperglycemia induced Egr-1 and vascular endothelial growth factor-A (VEGF-A) but not pigment epithelium derived factor (PEDF) in hRECs. Expression of Egr-1 repressor NGFI-A binding protein-2 (NAB-2) was unaltered. Egr-1 downstream gene targets, tissue factor (TF) and intercellular adhesion molecule-1 (ICAM-1) expression were increased in hRECs which was reduced by Egr-1 silencing in hyperglycemia. Diabetic retina, showed an increase in Egr-1, VEGF-A and gene target TF, ICAM-1 but not NAB-2 and PEDF similar to the changes seen in hyperglycemic hRECs. Hyperglycemic induction of Egr-1 and absence of NAB-2 repression in retinal endothelium, up-regulates downstream genes involved in pro-thrombotic and pro-inflammatory pathways linking Egr-1 in diabetes mediated vascular aberration of retina.


Asunto(s)
Retinopatía Diabética/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Células Endoteliales/metabolismo , Glucosa/metabolismo , Hiperglucemia/metabolismo , Vasos Retinianos/metabolismo , Células Cultivadas , Retinopatía Diabética/genética , Retinopatía Diabética/fisiopatología , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Células Endoteliales/efectos de los fármacos , Proteínas del Ojo/metabolismo , Glucosa/toxicidad , Humanos , Hiperglucemia/genética , Hiperglucemia/fisiopatología , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/fisiopatología , Serpinas/metabolismo , Transducción de Señal , Tromboplastina/genética , Tromboplastina/metabolismo , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo
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