The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform
Mark O.m. Tso - One of the best experts on this subject based on the ideXlab platform.
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Sinomenine inhibits activation of rat Retinal microglia induced by advanced glycation end products.
International immunopharmacology, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Ming Yuan, Mark O.m. TsoAbstract:Abstract Diabetic retinopathy involves an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. Thus, therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Sinomenine, an alkaloid isolated from the stem and root of Sinomenium acutum , has long been recognized as an anti-inflammatory drug for rheumatoid arthritis and also inhibits macrophage activation. In this study, we activated Retinal microglia in culture with advanced glycation end products (AGEs) treatment and attempted to determine whether sinomenine could reduce the production of cytokines from the activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF alpha, IL-1 beta and IL-6, were measured by semi-quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) both in the presence and absence of AGEs. The effect of sinomenine on levels of reactive oxygen species (ROS) and the nuclear translocation of NF-kB p65 were studied with a laser confocal scanning microscope. AGEs treatment induced a significant release of TNF alpha, IL-1beta, and IL-6 from Retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated Retinal microglia in culture.
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AGEs mediated expression and secretion of TNF alpha in rat Retinal microglia
Experimental eye research, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Mark O.m. TsoAbstract:Diabetic retinopathy induces an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and the activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following Retinal metabolic stress. We have previously shown that DR rats have elevated levels of advanced glycation end products (AGEs) in their blood. We have also suggested that AGEs might be involved in microglial activation and production of tumor necrosis factor alpha (TNF alpha). In this study, we attempted to confirm that AGEs induce the release of TNF alpha from rat Retinal microglia using an in vitro microglia culture system, and concurrently to explore the mediating mechanisms. AGEs increased the protein secretion and mRNA expression of TNF alpha in cultured rat Retinal microglia. These effects of AGEs were primarily mediated by reactive oxygen species (ROS). Furthermore, the inhibitors for mitogen-activated protein kinases (MAPK; p38, JNK and ERK 1/2) and nuclear factor-kB (NF-kB) could significantly decrease AGEs-induced TNF alpha release. AGEs-activated microglia showed an increase of NF-kB p65 nuclear translocation. These observations indicated that pathophysiological levels of AGEs may alter rat Retinal microglia function by up-regulating TNF alpha expression and release via enhanced formation of intracellular ROS. AGEs-induced ROS subsequently activates MAPK (p38, JNK and ERK1/2) and NF-kB.
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New Therapeutic Modalities of Retinal Laser Injury.
1992Co-Authors: Tim T. Lam, Mark O.m. TsoAbstract:Abstract : Efficacies of three different regimens of high dose of methylprednisolone (MP) treatment on laser-induced non-hemorrhage Retinal Injury and tissue plasminogen activator (t-PA) in sub-Retinal hemorrhage laser Injury were evaluated in a sub-human primate model and a rat model respectively. Clinical, histopathological, and morphometric criteria were employed for evaluating the efficacy of MP. High dose and prolonged treatment (4 days) was the most effective regimen while high dose for 8 hours showed limited effect in non-hemorrhagic Retinal Injury. Intravitreal t-PA showed no apparent beneficial effect in sub-Retinal hemorrhage after laser Injury. Hence, patients with laser Retinal Injury may benefit from high dose MP treatment for an appropriate period of time. Laser, Retina, Injury, Treatment, Corticosteroids, Methylprednisolone, tissue plasminogen activator, sub-Retinal hemorrhage, RA 3.
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New Therapeutic Modalities for Laser Retinal Injury
1991Co-Authors: Tim T. Lam, Mark O.m. TsoAbstract:Abstract : Two grades (II and III) of Retinal lesions were evaluated using clinical, histopathologic, and morphometric methods from 3 days up to 20 days after the laser insult. Morphometric parameters varied according to time and the energy of the laser used. Preliminary evaluation of the efficacy of high-dose, and continuous infusion of methylprednisolone was performed using a swivel- tethering system. Clinical study at 3 and 10 days after laser Injury suggested a dramatic beneficial effect when the drug was given at 24 hours before Injury and continued for 4 days. Preliminary histopathologic observation also suggested a protective effect of the treatment regimen. Morphometric analysis is underway. In addition, two human cases of laser Injury to the Retina were studied clinically as a basis for clinical application of therapeutic modalities. Laser; Retina; Injury; Treatment; Corticosteroids; Methylprednisolone; RA 3
Ai Ling Wang - One of the best experts on this subject based on the ideXlab platform.
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Sinomenine inhibits activation of rat Retinal microglia induced by advanced glycation end products.
International immunopharmacology, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Ming Yuan, Mark O.m. TsoAbstract:Abstract Diabetic retinopathy involves an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. Thus, therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Sinomenine, an alkaloid isolated from the stem and root of Sinomenium acutum , has long been recognized as an anti-inflammatory drug for rheumatoid arthritis and also inhibits macrophage activation. In this study, we activated Retinal microglia in culture with advanced glycation end products (AGEs) treatment and attempted to determine whether sinomenine could reduce the production of cytokines from the activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF alpha, IL-1 beta and IL-6, were measured by semi-quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) both in the presence and absence of AGEs. The effect of sinomenine on levels of reactive oxygen species (ROS) and the nuclear translocation of NF-kB p65 were studied with a laser confocal scanning microscope. AGEs treatment induced a significant release of TNF alpha, IL-1beta, and IL-6 from Retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated Retinal microglia in culture.
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AGEs mediated expression and secretion of TNF alpha in rat Retinal microglia
Experimental eye research, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Mark O.m. TsoAbstract:Diabetic retinopathy induces an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and the activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following Retinal metabolic stress. We have previously shown that DR rats have elevated levels of advanced glycation end products (AGEs) in their blood. We have also suggested that AGEs might be involved in microglial activation and production of tumor necrosis factor alpha (TNF alpha). In this study, we attempted to confirm that AGEs induce the release of TNF alpha from rat Retinal microglia using an in vitro microglia culture system, and concurrently to explore the mediating mechanisms. AGEs increased the protein secretion and mRNA expression of TNF alpha in cultured rat Retinal microglia. These effects of AGEs were primarily mediated by reactive oxygen species (ROS). Furthermore, the inhibitors for mitogen-activated protein kinases (MAPK; p38, JNK and ERK 1/2) and nuclear factor-kB (NF-kB) could significantly decrease AGEs-induced TNF alpha release. AGEs-activated microglia showed an increase of NF-kB p65 nuclear translocation. These observations indicated that pathophysiological levels of AGEs may alter rat Retinal microglia function by up-regulating TNF alpha expression and release via enhanced formation of intracellular ROS. AGEs-induced ROS subsequently activates MAPK (p38, JNK and ERK1/2) and NF-kB.
Rafael Ufret-vincenty - One of the best experts on this subject based on the ideXlab platform.
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A Mouse Model of Retinal Recovery From Photo-Oxidative/Photo-Inflammatory Injury: Nrf2, SOD1, DJ-1, and Parkin Are Not Essential to Recovery.
Investigative ophthalmology & visual science, 2019Co-Authors: Bo Chen, Bogale Aredo, Yuanfei Zhu, Yi Ding, Cynthia Xin-zhao, Rafael Ufret-vincentyAbstract:Purpose To determine if there is structural and functional recovery of the Retina from light induced Retinal degeneration, and to evaluate the role of the oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin in such a recovery process. Methods Eyes from C57BL/6J (B6J) mice and from oxidative stress response-deficient strains of mice were treated with intense light using the fundus camera-delivered light-induced Retinal degeneration (FCD-LIRD) model. Fundus photographs, optical coherence tomography (OCT) images, and electroretinography (ERG) responses were obtained before the Injury, during the "maximal Injury phase" (days 4-7) and during the "recovery phase" (days 14-16) post light exposure and were evaluated for Retinal damage and assessed for evidence of recovery from the Injury. Results We demonstrate that mice treated with a sub-lethal FCD-LIRD protocol show an initial acute Retina Injury phase peaking between days 4 to 7 followed by a recovery phase in which the outer Retinal thickness/volume and Retinal function partially recover. These observations are reproduced in B6J mice and in mice lacking oxidative stress response enzymes (SOD1, DJ-1, and Parkin) or the oxidative stress response master regulator Nrf2. Conclusions Our data indicate that Retinal recovery from Injury can proceed via pathways that are independent from the common oxidative stress response elements Nrf2, SOD1, DJ-1, and Parkin. Furthermore, the model of Retinal recovery from Injury that we describe here mimics changes seen in a variety of clinical entities and may provide an excellent platform for dissecting general pathways of Retinal recovery from sub-lethal Injury.
Dale S. Gregerson - One of the best experts on this subject based on the ideXlab platform.
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Dendritic cells are early responders to Retinal Injury.
Neurobiology of disease, 2010Co-Authors: Ute Lehmann, Neal D. Heuss, Scott W. Mcpherson, Heidi Roehrich, Dale S. GregersonAbstract:The presence and activity of dendritic cells (DC) in Retina is controversial, as these cells are difficult to identify in Retina due to limited markers and sparse numbers. Transgenic mice that express green fluorescent protein (GFP) on the CD11c promoter to label DC allowed the visualization and quantification of Retinal DC. Two Retina Injury models, the optic nerve crush (ONC) and light Injury, were used to study their Injury response. Many GFP+ DC were tightly associated with Retinal ganglion cell nerve fibers following ONC, while very few microglia (GFP−CD11b+ cells) were found in close contact. The GFP+ cells were greatly elevated in the outer plexiform layer following photic Injury. All of the GFP+ DC were CD11b+, suggesting a myeloid origin. In addition, the GFP+ DC upregulated expression of MHC class II after Injury, while the GFP−CD11b+ microglia did not. This study shows that DC were found in the Retina and that they rapidly responded to neural injuries. We propose that they are a previously overlooked population, distinct from microglia, and may be important in the Injury response.
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Engrafted neural progenitor cells express a tissue-restricted reporter gene associated with differentiated Retinal photoreceptor cells.
Cell transplantation, 2006Co-Authors: Thien N. Sam, Heidi Roehrich, Jing Xiao, Walter C. Low, Dale S. GregersonAbstract:Neural progenitor cells (NPCs) have shown ability to repair injured CNS, and might provide precursors to Retinal neurons. NPCs were isolated from the brains of 14 day murine embryos of transgenic mice that express beta-galactosidase (beta-gal) on the arrestin promoter, which specifically directs expression to Retinal photoreceptor cells. NPCs were transferred to adult, syngeneic mice via inoculation into the anterior chamber of the eye, the peritoneal cavity, or the brain. At 14 weeks postgrafting, tissues were collected and examined to determine if differentiated NPC progeny were present in Retina based on histochemical detection of beta-gal. Four of six anterior chamber-inoculated recipients showed Bluo-gal-stained cells in Retina, indicating the presence of transferred NPCs or their progeny. Because the progenitor cells do not express beta-gal, positive staining indicates differentiation leading to activation of the arrestin promoter. Two recipients inoculated by the intraperitoneal route also exhibited Bluo-gal staining in Retina. The NPCs did not express beta-gal if inoculated into brain, but survived and dispersed. Most recipients, regardless of inoculation route, were PCR positive for beta-gal DNA in extraocular tissues, but no Bluo-gal staining was found outside of the Retina. Injury to the Retina promoted, but was not required, for progenitor cell engraftment. beta-Gal-positive cells were concentrated in the outer layers of the Retina. In summary, a reporter gene specifically expressed in differentiated Retinal photoreceptor cells due to the activity of the arrestin promoter was expressed in recipient mouse Retina following transfer of NPCs prepared from the beta-gal transgenic mice. The presence of beta-gal DNA, but not Bluo-gal staining, in spleen and other tissues revealed that the cells also migrated elsewhere and took up residence in other organs, but did not undergo differentiation that led to beta-gal expression.
Xiu'an Zhu - One of the best experts on this subject based on the ideXlab platform.
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Sinomenine inhibits activation of rat Retinal microglia induced by advanced glycation end products.
International immunopharmacology, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Ming Yuan, Mark O.m. TsoAbstract:Abstract Diabetic retinopathy involves an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. Thus, therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Sinomenine, an alkaloid isolated from the stem and root of Sinomenium acutum , has long been recognized as an anti-inflammatory drug for rheumatoid arthritis and also inhibits macrophage activation. In this study, we activated Retinal microglia in culture with advanced glycation end products (AGEs) treatment and attempted to determine whether sinomenine could reduce the production of cytokines from the activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF alpha, IL-1 beta and IL-6, were measured by semi-quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) both in the presence and absence of AGEs. The effect of sinomenine on levels of reactive oxygen species (ROS) and the nuclear translocation of NF-kB p65 were studied with a laser confocal scanning microscope. AGEs treatment induced a significant release of TNF alpha, IL-1beta, and IL-6 from Retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated Retinal microglia in culture.
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AGEs mediated expression and secretion of TNF alpha in rat Retinal microglia
Experimental eye research, 2007Co-Authors: Ai Ling Wang, Xiu'an Zhu, Mark O.m. TsoAbstract:Diabetic retinopathy induces an inflammatory response in the Retina characterized by an increase in inflammatory cytokines and the activation of microglia. The degree of microglia activation may influence the extent of Retina Injury following Retinal metabolic stress. We have previously shown that DR rats have elevated levels of advanced glycation end products (AGEs) in their blood. We have also suggested that AGEs might be involved in microglial activation and production of tumor necrosis factor alpha (TNF alpha). In this study, we attempted to confirm that AGEs induce the release of TNF alpha from rat Retinal microglia using an in vitro microglia culture system, and concurrently to explore the mediating mechanisms. AGEs increased the protein secretion and mRNA expression of TNF alpha in cultured rat Retinal microglia. These effects of AGEs were primarily mediated by reactive oxygen species (ROS). Furthermore, the inhibitors for mitogen-activated protein kinases (MAPK; p38, JNK and ERK 1/2) and nuclear factor-kB (NF-kB) could significantly decrease AGEs-induced TNF alpha release. AGEs-activated microglia showed an increase of NF-kB p65 nuclear translocation. These observations indicated that pathophysiological levels of AGEs may alter rat Retinal microglia function by up-regulating TNF alpha expression and release via enhanced formation of intracellular ROS. AGEs-induced ROS subsequently activates MAPK (p38, JNK and ERK1/2) and NF-kB.