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Antje Grosche - One of the best experts on this subject based on the ideXlab platform.
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Effects of IP_3R2 Receptor Deletion in the Ischemic Mouse Retina
Neurochemical Research, 2016Co-Authors: Lysann Wagner, Thomas Pannicke, Ina Frommherz, Katja Sauer, Ju Chen, Antje GroscheAbstract:Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of Retinal Müller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K^+ current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y_1 leads to an altered regulation of K^+ currents in Müller cells of the ischemic Retina. Here, we asked first whether this effect is mediated by the IP_3 receptor subtype 2 (IP_3R2) known as the major downstream signaling target of P2Y_1 in Müller cells. The second question was whether lack of IP_3R2 affects neuronal survival in the control and ischemic Retina. Ischemia was induced in wild type and IP_3R2-deficient ( IP _ 3 R2 ^− / −) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K^+ currents in Müller cells from ischemic IP _ 3 R2 ^− / − Retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after Ischemia was similar in wild type and IP _ 3 R2 ^− / − mice. However, IP_3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after Ischemia. This implies that IP_3R2 is involved in some but not all aspects of signaling in Müller cells after an ischemic insult.
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Effects of IP3R2 Receptor Deletion in the Ischemic Mouse Retina.
Neurochemical research, 2015Co-Authors: Lysann Wagner, Thomas Pannicke, Ina Frommherz, Katja Sauer, Ju Chen, Antje GroscheAbstract:Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of Retinal Muller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K+ current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y1 leads to an altered regulation of K+ currents in Muller cells of the ischemic Retina. Here, we asked first whether this effect is mediated by the IP3 receptor subtype 2 (IP3R2) known as the major downstream signaling target of P2Y1 in Muller cells. The second question was whether lack of IP3R2 affects neuronal survival in the control and ischemic Retina. Ischemia was induced in wild type and IP3R2-deficient (IP 3 R2 −/−) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K+ currents in Muller cells from ischemic IP 3 R2 −/− Retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after Ischemia was similar in wild type and IP 3 R2 −/− mice. However, IP3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after Ischemia. This implies that IP3R2 is involved in some but not all aspects of signaling in Muller cells after an ischemic insult.
Neville N. Osborne - One of the best experts on this subject based on the ideXlab platform.
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Expression of prostaglandin PGE2 receptors under conditions of aging and stress and the protective effect of the EP2 agonist butaprost on Retinal Ischemia.
Investigative ophthalmology & visual science, 2009Co-Authors: Neville N. Osborne, Belmira Lara Da Silveira Andrade Da Costa, Rebecca J. Fawcett, Kui Dong Kang, Kay D. RittenhouseAbstract:PURPOSE. To localize different prostaglandin E 2 receptors in rat Retinas of varying age, deduce how they are affected by acute stress insult, and determine whether the negative effect of Ischemia/reperfusion is attenuated by the EP2 agonist butaprost. METHODS. Ischemia was induced by the elevation of intraocular pressure. Butaprost was injected intravitreally immediately after Ischemia. Standard methods were used for recording of electroretinograms (ERGs) and processing of immunohistochemistry. Extracts of whole Retinas were analyzed for specific proteins by Western blotting or by RT-PCR for defined mRNAs. RESULTS. The localization of different EP receptor types is similar in Retinas of all aged rats. However, differences exist in the monomer/dimer ratios in Retinas of different age. Acute stress insult (48 hours after Ischemia) affects the ratio of monomer/ dimer of all EP receptor types and increases EP2 and EP3 immunoreactivities in Muller cells of the adult Retina. Ischemia and 5 to 7 days of reperfusion to the Retina caused the normal ERG and the localization of nNOS and ChAT immunoreactivities to be affected. Certain proteins and mRNAs were lowered in content, whereas other proteins and mRNAs were upregulated. In addition, specific optic nerve proteins were drastically reduced. Most of these changes induced by Ischemia/reperfusion were significantly blunted by butaprost. CONCLUSIONS. All subtypes of EP receptors exist primarily in the inner Retina at different ages, but their monomer/dimer ratios vary. Stress affects the monomer/dimer ratio and EP2 and EP3 immunoreactivities in Muller cells. Butaprost injected intravitreally significantly blunts the detrimental influence of Ischemia/reperfusion to the Retina.
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Orally administered epigallocatechin gallate attenuates Retinal neuronal death in vivo and light-induced apoptosis in vitro.
Brain research, 2007Co-Authors: Bo Zhang, Dario Rusciano, Neville N. OsborneAbstract:The aim of this study was to provide support for epigallocatechin gallate (EGCG), a component of green tea, to be considered in the context for neuroprotection in glaucoma, where administration by an oral route is required for adequate penetration into the Retina. Ischemia was delivered to one eye of a number of rats by raising the intraocular pressure. EGCG was present in the drinking water of half of the animals 3 days before Ischemia and also during the next 5 days of reperfusion. The electroretinograms (ERGs) of both eyes from all rats were recorded before Ischemia and 5 days following Ischemia. Seven days after Ischemia Retinas from both eyes of all rats were either analysed for the localisation of various antigens or extracts prepared for analysis for the level of specific proteins and mRNAs. Ischemia/reperfusion to the Retina affected a number of parameters. These included the localisation of Thy-1 and choline acetyltransferase, the a- and b-wave amplitudes of the ERG, the content of certain Retinal and optic nerve proteins and various mRNAs. Significantly, EGCG statistically blunted many of the effects induced by Ischemia/reperfusion which included the activation of caspases. These studies demonstrate conclusively that orally administered EGCG attenuates injury to the Retina caused by Ischemia/reperfusion where caspases were activated. Studies were also conducted on a cell line (RGC-5 cells) where it was shown that white light (1000 lx, 48 h)-induced apoptosis is caspase-independent and can be blunted by EGCG. The present studies support the view for the use of EGCG in the treatment of glaucoma based on the premise that any potential neuroprotective agent must be administered orally, have a safe profile and poses a broad spectrum of properties that allows various risk factors (that include Ischemia and light) to be attenuated.
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Memantine reduces alterations to the mammalian Retina, in situ, induced by Ischemia.
Visual neuroscience, 1999Co-Authors: Neville N. OsborneAbstract:The aim of the study was to determine whether memantine could slow down the changes seen in the rabbit and rat Retina following Ischemia/reperfusion. A “suction cup procedure,” which raises the intraocular pressure, was used to give an ischemic insult to the rabbit Retina. The electroretinogram was recorded before Ischemia and after 2 days of reperfusion. Memantine or saline (10 μl) was injected into the eye before Ischemia. Immunohistochemistry was used to study the effect of Ischemia/reperfusion on the GABA, ChAT, and αPKC immunoreactivities. Ischemia/reperfusion injury to the rat Retina was induced by raising the intraocular pressure above the systolic blood pressure for 60 min, followed by reperfusion of 3–14 days. Memantine (5 mg/kg) or saline was injected i.p. at the onset of Ischemia or reperfusion. Immunohistochemistry was used to study the effect of Ischemia/reperfusion on the ChAT, αPKC, and Thy-1 immunoreactivities. In addition, morphometric analysis was carried out to determine the effects of Ischemia/reperfusion on the thickness of the Retina. Ischemia for 75 min caused a change in the nature of the normal GABA and ChAT immunoreactivities in the rabbit Retina and a reduction in the b -wave of the electroretinogram. When memantine was injected into the vitreous humour at the onset of an ischemic insult, the changes in the GABA and ChAT immunoreactivities were reduced and the recovery of the reduced b -wave of the electroretinogram after 2 days reperfusion was enhanced significantly. Ischemia for 60 min followed by 3 days reperfusion showed a clear change in ChAT immunoreactivity in the rat Retina. The Thy-1 immunoreactivity was only clearly altered after a reperfusion period of 7 days. Moreover, a measurable change in the thickness of the inner Retinal layers was detected after 14 days of reperfusion. When given at the onset of Ischemia, memantine counteracted the effect of Ischemia/reperfusion to varying degrees. However, when memantine was given at the onset of the reperfusion this was not the case. The combined data show that a single injection of memantine given i.p. or intravitreally will protect the Retina from a subsequent ischemic insult.
Lysann Wagner - One of the best experts on this subject based on the ideXlab platform.
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Effects of IP_3R2 Receptor Deletion in the Ischemic Mouse Retina
Neurochemical Research, 2016Co-Authors: Lysann Wagner, Thomas Pannicke, Ina Frommherz, Katja Sauer, Ju Chen, Antje GroscheAbstract:Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of Retinal Müller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K^+ current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y_1 leads to an altered regulation of K^+ currents in Müller cells of the ischemic Retina. Here, we asked first whether this effect is mediated by the IP_3 receptor subtype 2 (IP_3R2) known as the major downstream signaling target of P2Y_1 in Müller cells. The second question was whether lack of IP_3R2 affects neuronal survival in the control and ischemic Retina. Ischemia was induced in wild type and IP_3R2-deficient ( IP _ 3 R2 ^− / −) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K^+ currents in Müller cells from ischemic IP _ 3 R2 ^− / − Retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after Ischemia was similar in wild type and IP _ 3 R2 ^− / − mice. However, IP_3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after Ischemia. This implies that IP_3R2 is involved in some but not all aspects of signaling in Müller cells after an ischemic insult.
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Effects of IP3R2 Receptor Deletion in the Ischemic Mouse Retina.
Neurochemical research, 2015Co-Authors: Lysann Wagner, Thomas Pannicke, Ina Frommherz, Katja Sauer, Ju Chen, Antje GroscheAbstract:Glial cells in the diseased nervous system undergo a process known as reactive gliosis. Gliosis of Retinal Muller glial cells is characterized by an upregulation of glial fibrillary acidic protein and frequently by a reduction of inward K+ current amplitudes. Purinergic signaling is assumed to be involved in gliotic processes. As previously shown, lack of the nucleotide receptor P2Y1 leads to an altered regulation of K+ currents in Muller cells of the ischemic Retina. Here, we asked first whether this effect is mediated by the IP3 receptor subtype 2 (IP3R2) known as the major downstream signaling target of P2Y1 in Muller cells. The second question was whether lack of IP3R2 affects neuronal survival in the control and ischemic Retina. Ischemia was induced in wild type and IP3R2-deficient (IP 3 R2 −/−) mice by transient elevation of the intraocular pressure. Immunostaining and TUNEL labelling were used to quantify neuronal cell loss. The downregulation of inward K+ currents in Muller cells from ischemic IP 3 R2 −/− Retinae was less strong than in wild type animals. The reduction of the number of cells in the ganglion cell layer and of calretinin- and calbindin-positive cells 7 days after Ischemia was similar in wild type and IP 3 R2 −/− mice. However, IP3R2 deficiency led to an increased number of TUNEL-positive cells in the outer nuclear layer at 1 day and to an enhanced postischemic loss of photoreceptors 7 days after Ischemia. This implies that IP3R2 is involved in some but not all aspects of signaling in Muller cells after an ischemic insult.
Meng Rui-hu - One of the best experts on this subject based on the ideXlab platform.
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The protective effect of puerarin to Retina Ischemia-reperfusion injure
Clinical Ophthalmology, 2007Co-Authors: Meng Rui-huAbstract:Objective To study the protective effect and mechanisms of puerarin to Retina Ischemia-reperfusion (RIR) injure. Method Adult wistar in spite of male or female rates were randomly assigned to 3 groups:control,Ischemia-reperfusion,Ischemia-referfusion+Pur group.The modle of IRI were accomplished in Wistar rates by increasing the intraocular pressure to 14.33Kp for 1 hour via cannulation into anterior chamber.rats were treated with 0.5g/kg puerarin before operation by intrapertoneal injected. Retinal histological changes were observes,the number of RGCs and the leukocyte infiltrating in Retinal were counted,and image analysis system was usesd to detect the thickness of inner Retinal layer.The expression of Caspase-3 was assessed by immunohistlchemistry. Results Every stage after 6 hours of RIR, The inner layers of Retina of the treated was thicker than the untreated. while at the later stage the decrease of RGCs number and the atrophy and thinning of nerve fiber layer were the main changer.During the early period of reperfusion, the edema of Retina was reduced in treatment group than the Ischemia. The number of RGCs of treatment group was more and the number of leukocyte was less than the untreated.The expression of Caspase-3 began to increase at 6th hour and reached the peak at 24th.With the reperfusion time prolonged,it began to deceased.The expression of the treated group was relatively obvious less than the untreated. Conclusion Puerarin has therapeutical effect to Retinal Ischemia-reperfusion injure.The possible protective mechanism is that puerarin can downregulate Caspase-3 expression and decrease inflammatory reaction induced by Retinal Ischemia-reperfusion.
Hsiao-ming Chao - One of the best experts on this subject based on the ideXlab platform.
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Xue-fu-Zhu-Yu decoction protects rats against Retinal Ischemia by downregulation of HIF-1α and VEGF via inhibition of RBP2 and PKM2.
BMC complementary and alternative medicine, 2017Co-Authors: Shu-qiu Tan, Jorn-hon Liu, Xue Geng, Wynn Hwai-tzong Pan, Li-xiang Wang, Hui-kang Liu, Hsiao-ming ChaoAbstract:Retinal Ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to Retinal Ischemia. Retinal Ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed. Significant ischemic changes occurred after Ischemia including decreased ERG b-wave ratios, less numerous Retinal ganglion cells (RGCs), reduced inner Retinal thickness, fewer choline acetyltransferase (ChAT) labeled amacrine cell bodies, increased glial fibrillary acidic protein (GFAP) immunoreactivity and increased vimentin Muller immunolabeling. These were accompanied by significant increases in the mRNA/protein concentrations of vascular endothelium growth factor, hypoxia-inducible factor-1α, pyruvate kinase M2 and retinoblastoma-binding protein 2. The ischemic changes were concentration-dependently and significantly altered when XFZYD was given for seven consecutive days before or after Retina Ischemia, compared to vehicle. These alterations included enhanced ERG b-wave amplitudes, more numerous RGCs, enhanced inner Retinal thickness, a greater number of ChAT immunolabeled amacrine cell bodies and decreased GFAP/vimentin immunoreactivity. Furthermore, decreased mRNA levels of VEGF, HIF-1α, PKM2, and RBP2 were also found. Reduced protein concentrations of VEGF, HIF-1α, PKM2, and RBP2 were also demonstrated. Furthermore, there was an inhibition of the Ischemia-associated increased ratios (target protein/β-actin) in the protein levels of VEGF, HIF-1α, PKM2, and RBP2, which were induced by Shikonin, JIB-04 or Avastin. XFZYD would seem to protect against well-known Retinal ischemic changes via a synergistic inhibition of RBP2 and PKM2, as well as down-regulation of HIF-1α and a reduction in VEGF secretion.
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the effects and underlying mechanisms of s allyl l cysteine treatment of the Retina after Ischemia reperfusion
Journal of Ocular Pharmacology and Therapeutics, 2012Co-Authors: Yan-qing Chen, Wynn H.t. Pan, Jorn-hon Liu, Mi-mi Chen, Chi-ming Liu, Ming-yang Yeh, Shen-kou Tsai, Mason Shing Young, Xiu-mei Zhang, Hsiao-ming ChaoAbstract:Abstract Purpose: Retinal Ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against Retina Ischemia/reperfusion injury. Methods: In vivo, Retinal Ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating Retinal ganglion cell-5 (RGC-5) with 500 μM H2O2 for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches. Results: The Retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The i...
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The effects and underlying mechanisms of S-allyl l-cysteine treatment of the Retina after Ischemia/reperfusion.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2011Co-Authors: Yan-qing Chen, Wynn H.t. Pan, Jorn-hon Liu, Mi-mi Chen, Chi-ming Liu, Ming-yang Yeh, Shen-kou Tsai, Mason Shing Young, Xiu-mei Zhang, Hsiao-ming ChaoAbstract:Abstract Purpose: Retinal Ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against Retina Ischemia/reperfusion injury. Methods: In vivo, Retinal Ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating Retinal ganglion cell-5 (RGC-5) with 500 μM H2O2 for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches. Results: The Retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The i...