BDNF对鼠视网膜Miiller细胞GLAST和GS调控作用的研究
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摘要
目的研究BDNF对正常氧状态下的鼠视网膜Miiller细胞谷氨酸转运体GLAST和谷氨酰胺合成酶GS表达及功能的调控作用。
方法取出生3-7天的新生昆明小鼠视网膜组织进行正常氧状态下Muller细胞培养,取传代后第三代Muller细胞进行后续实验。实验分为BDNF干预组：鼠视网膜Muller细胞分别加入50、75、100、125和150ng/ml的BDNF培养24h；正常对照组：培养的Muller细胞中不加BDNF。采用逆转录聚合酶链反应(RT-PCR)方法检测Muller细胞GLAST及GSmRNA的表达；采用Western blot(?)阳免疫细胞化学染色方法检测Muller细胞GLAST及GS蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测100ng/ml的BDNF干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异。
结果不同浓度的BDNF均能上调GLAST及GS的表达(P<0.05),并且随着BDNF浓度的增大,GLAST及GS的表达量增加,当BDNF浓度为100ng/ml时,GLAST及GS表达最强。免疫细胞化学染色显示GLAST蛋白主要定位于Muller细胞胞浆及胞膜上,GS蛋白主要定位于Muller细胞胞浆中。不同浓度的BDNF作用于Muller细胞后,GLAST及GS蛋白表达增强。100ng/ml的BDNF能够明显增加Muller细胞对谷氨酸的摄取(P<0.05)。
结论在正常氧状态下,BDNF能够上调Muller细胞中GLAST和GS的表达,并且增加Muller细胞对细胞外谷氨酸的摄取。
目的研究缺氧对鼠视网膜Muller细胞谷氨酸转运体GLAST和谷氨酰胺合成酶GS表达及功能的影响。
方法采用出生3-7天的小鼠视网膜组织进行Muller细胞培养,采用125μmol/L的氯化钴(CoCl2)溶液分别进行缺氧干预6h、12h、24h、48h和72h；不加CoCl2溶液培养的Muller细胞为正常对照组。采用RT-PCR方法检测Muller细胞GLAST及GS mRNA的表达；采用Western blot和免疫细胞化学染色方法检测Muller细胞GLAST及GS蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测CoCl2溶液缺氧干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异；采用Annexin Ⅴ-FITC细胞凋亡检测试剂盒检测细胞凋亡情况。
结果缺氧早期GLAST表达较正常对照组明显增强(P<0.001),CoCl2溶液干预12h后达到最强(P<0.05),之后逐渐降低,CoCl2溶液干预72h后GLAST表达与正常对照组相比无明显差异(P>0.05)。缺氧也使GS的表达较正常对照组增加(P<0.001),CoCl2溶液干预48h后GS表达最强(P<0.001),之后开始下降。缺氧促进Muller细胞对谷氨酸的摄取,CoCl2溶液干预48h后L-[3,4-H3]-谷氨酸的摄取量最大(P<0.005),之后开始下降。而CoCl2溶液干预后,Muller细胞死亡数较正常对照组无明显差异(P>0.05)。
结论在一定时间范围内缺氧能够上调Miiller细胞GLAST及GS的表达,增加谷氨酸的摄取。但持续缺氧最终会引起Muller细胞功能失代偿,从而导致谷氨酸的代谢能力降低。
目的研究BDNF对缺氧状态下鼠视网膜Muller细胞谷氨酸转运体GLAST和谷氨酰胺合成酶GS表达及功能的调控作用。
方法采用出生3-7天的小鼠视网膜组织进行Muller细胞培养,采用125μmol/L的CoCl2溶液干预72h,同时采用100ng/ml的BDNF分别干预24h、48h、72h和96h；采用125μmol/L的CoCl2溶液干预72h的Muller细胞为缺氧对照组；不加CoCl2溶液及BDNF的Muller细胞为正常对照组。采用RT-PCR方法检测Muller细胞GLAST及GS mRNA的表达；采用Western blot和免疫细胞化学染色方法检测Muller细胞GLAST蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测CoCl2溶液缺氧干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异；采用Annexin Ⅴ-FITC细胞凋亡检测试剂盒检测细胞凋亡情况。
结果与缺氧对照组及正常对照组相比,CoCl2缺氧干预后加入BDNF干预各组(24h、48h、72h),GLAST及GS的表达上调(P<0.05),其中以CoCl2缺氧干预72h,BDNF干预48h组GLAST及GS表达最强(P<0.05)。然而,CoCl2缺氧干预72h,BDNF干预96h组,GLAST及GS的表达与缺氧对照组及正常对照组无明显差异(P>0.05)。CoCl2缺氧干预后加入BDNF干预各组(24h、48h、72h)与缺氧对照组及正常对照组相比,Muller细胞对谷氨酸的摄取量增加(P<0.05),以CoCl2缺氧干预72h,BDNF干预48h组谷氨酸的摄取量最大(P<0.05)。加入CoCl2溶液及BDNF干预后,Muller细胞死亡数较正常对照组无明显差异(P>0.05)。
结论BDNF能够上调缺氧状态下视网膜Muller细胞GLAST及GS的表达,并增加Muller细胞对细胞外谷氨酸的摄取。
Chapterl Effect of BDNF on the GLAST and GS in mouse retinal Miiller cells under normal oxygen condition
Objective:To study the effect of brain-derived neurotrophic factor (BDNF) on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Miiller cells (RMCs) under normal oxygen conditions.
Methods:Retinal Miiller cells (RMCs) of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs passaged three times were used in next experiments. RMCs cultures were divided into BDNF group:Cultured retinal Muller cells were maintained with different concentrations of recombinant human BDNF (50ng/ml,75ng/ml,100ng/ml,125ng/ml or150ng/ml)for24h in vitro, and Control group:Cultured retinal Muller cells were maintained without BDNF. The expression of GLAST and GS mRNA was measured by RT-PCR. The expression of GLAST and GS protein was measured by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs in BDNF group (100ng/ml) and normal control group.
Results:Different concentrations of BDNF could up-regulate GLAST and GS expression compared to normal control (p<0.05). The expression of GLAST and GS reached the maximum when the concentration of BDNF was100ng/ml. Immunocytochemistry demonstra-ted that GLAST was predominantly found in the membrane and cytoplasm, while GS was predominantly found in the cytoplasm. Both GLAST and GS immunostaining appeared more intense in BDNF-treated cells. L-[3,4-3H]-glutamic acid uptake of BDNF group (100ng/ml) was significantly higher than normal control group.
Conclusion:BDNF may up-regulate GLAST and GS expression to increase extracellular glutamate uptake under normal oxygen conditions.
Chapter2Effect of hypoxia on the GLAST and GS in mouse retinal Muller cells
Objective:This study investigated the effect of hypoxia on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Muller cells (RMCs)
Methods:RMCs of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs cultures were treated with CoCl2(125μmol/L) for6h,12h,24h,48h or72h respectively in vitro. RMCs cultures were maintained without CoCl2in normal control group. The expression of GLAST and GS mRNA was determined by RT-PCR. The expression of GLAST and GS protein was determined by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs. The apoptosis of RMCs was confirmed by annexin V-FITC/PI staining.
Results:In early-stage of CoCl2-induced hypoxia (treated with CoCl2for6h,12h,24h or48h), the expression of GLAST was up-regulated (p<0.001) and reached the maximum when RMCs have been treated with CoCl2for12h (p<0.05). After RMCs have been treated with CoCl2for72h, the expression of GLAST had no difference compared to normal control (p>0.05). CoCl2-induced hypoxia (treated with CoCl2for6h,12h,24h,48h or72h) also up-regulated the expression of GS (p<0.001), which reached the maximum when RMCs have been treated with CoCl2for48h (p<0.001). The L-[3,4-3H]-glutamic acid uptake of hypoxia groups were higher than normal control group (p<0.05), and after having treated RMCs with CoCl2for48h, the L-[3,4-3H]-glutamic acid uptake was highest (p<0.005). Treatments with CoCl2did not induce apoptosis in RMCs.
Conclusion:In early hypoxia stage, GLAST and GS may be up-regulated and extracellular glutamate uptake may be increased. However, continued hypoxia may cause gradual dysfunction and decreasing of GLAST and GS expression, as well as glutamate uptake.
Chapter3Effect of BDNF on the GLAST and GS in mouse retinal Miiller cells under hypoxia
Objective:To study the effect of brain-derived neurotrophic factor (BDNF) on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Miiller cells (RMCs) under hypoxia.
Method:RMCs of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs cultures were treated with CoCl2(125μmol/L) for72h, then combined with BDNF (100ng/ml) for24,48,72, or96h. RMCs cultures were maintained without CoCl2and BDNF in normal controls, RMCs cultures were maintained with CoCl2for72h in hypoxia controls. The expression of GLAST and GS mRNA was determined by RT-PCR. The expression of GLAST and GS protein was determined by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs. The apoptosis of RMCs was confirmed by annexin V-FITC/PI staining.
Result:BDNF treatment increased GLAST and GS mRNA and protein levels compared to nomal controls (p<0.001) and to hypoxia controls (p<0.05). Maximum protection was observed at48h after BDNF treatment (p<0.05), However, when BDNF treatment occurred at24h before CoCl2treatment, GLAST and GS expression had no difference compared to normal controls (p>0.05). Both GLAST and GS immunostaining appeared more intense when BDNF treatment occurred after CoCl2treatment, but not when BDNF treatment occurred at24h before CoCl2treatment. At72h after hypoxia, BDNF treatment also increased L-[3,4-3H]-glutamic acid uptake compared to nomal controls (p <0.001) and hypoxia controls (p<0.005), and this effect was maximal at48h after BNDF treatment. Hypoxia combined with BNDF had not induce death (apoptotic and necrotic) of RMCs compared with controls (p>0.05).
Conclusion:BDNF may up-regulate GLAST and GS expression and increase extracellular glutamate uptake in RMCs under hypoxia, but BDNF treatment has no effect at24h before hypoxia.
方法取出生3-7天的新生昆明小鼠视网膜组织进行正常氧状态下Muller细胞培养,取传代后第三代Muller细胞进行后续实验。实验分为BDNF干预组：鼠视网膜Muller细胞分别加入50、75、100、125和150ng/ml的BDNF培养24h；正常对照组：培养的Muller细胞中不加BDNF。采用逆转录聚合酶链反应(RT-PCR)方法检测Muller细胞GLAST及GSmRNA的表达；采用Western blot(?)阳免疫细胞化学染色方法检测Muller细胞GLAST及GS蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测100ng/ml的BDNF干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异。
结果不同浓度的BDNF均能上调GLAST及GS的表达(P<0.05),并且随着BDNF浓度的增大,GLAST及GS的表达量增加,当BDNF浓度为100ng/ml时,GLAST及GS表达最强。免疫细胞化学染色显示GLAST蛋白主要定位于Muller细胞胞浆及胞膜上,GS蛋白主要定位于Muller细胞胞浆中。不同浓度的BDNF作用于Muller细胞后,GLAST及GS蛋白表达增强。100ng/ml的BDNF能够明显增加Muller细胞对谷氨酸的摄取(P<0.05)。
结论在正常氧状态下,BDNF能够上调Muller细胞中GLAST和GS的表达,并且增加Muller细胞对细胞外谷氨酸的摄取。
目的研究缺氧对鼠视网膜Muller细胞谷氨酸转运体GLAST和谷氨酰胺合成酶GS表达及功能的影响。
方法采用出生3-7天的小鼠视网膜组织进行Muller细胞培养,采用125μmol/L的氯化钴(CoCl2)溶液分别进行缺氧干预6h、12h、24h、48h和72h；不加CoCl2溶液培养的Muller细胞为正常对照组。采用RT-PCR方法检测Muller细胞GLAST及GS mRNA的表达；采用Western blot和免疫细胞化学染色方法检测Muller细胞GLAST及GS蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测CoCl2溶液缺氧干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异；采用Annexin Ⅴ-FITC细胞凋亡检测试剂盒检测细胞凋亡情况。
结果缺氧早期GLAST表达较正常对照组明显增强(P<0.001),CoCl2溶液干预12h后达到最强(P<0.05),之后逐渐降低,CoCl2溶液干预72h后GLAST表达与正常对照组相比无明显差异(P>0.05)。缺氧也使GS的表达较正常对照组增加(P<0.001),CoCl2溶液干预48h后GS表达最强(P<0.001),之后开始下降。缺氧促进Muller细胞对谷氨酸的摄取,CoCl2溶液干预48h后L-[3,4-H3]-谷氨酸的摄取量最大(P<0.005),之后开始下降。而CoCl2溶液干预后,Muller细胞死亡数较正常对照组无明显差异(P>0.05)。
结论在一定时间范围内缺氧能够上调Miiller细胞GLAST及GS的表达,增加谷氨酸的摄取。但持续缺氧最终会引起Muller细胞功能失代偿,从而导致谷氨酸的代谢能力降低。
目的研究BDNF对缺氧状态下鼠视网膜Muller细胞谷氨酸转运体GLAST和谷氨酰胺合成酶GS表达及功能的调控作用。
方法采用出生3-7天的小鼠视网膜组织进行Muller细胞培养,采用125μmol/L的CoCl2溶液干预72h,同时采用100ng/ml的BDNF分别干预24h、48h、72h和96h；采用125μmol/L的CoCl2溶液干预72h的Muller细胞为缺氧对照组；不加CoCl2溶液及BDNF的Muller细胞为正常对照组。采用RT-PCR方法检测Muller细胞GLAST及GS mRNA的表达；采用Western blot和免疫细胞化学染色方法检测Muller细胞GLAST蛋白质的表达；采用L-[3,4-H3]-谷氨酸检测CoCl2溶液缺氧干预组与正常对照组Muller细胞对谷氨酸的摄取功能的差异；采用Annexin Ⅴ-FITC细胞凋亡检测试剂盒检测细胞凋亡情况。
结果与缺氧对照组及正常对照组相比,CoCl2缺氧干预后加入BDNF干预各组(24h、48h、72h),GLAST及GS的表达上调(P<0.05),其中以CoCl2缺氧干预72h,BDNF干预48h组GLAST及GS表达最强(P<0.05)。然而,CoCl2缺氧干预72h,BDNF干预96h组,GLAST及GS的表达与缺氧对照组及正常对照组无明显差异(P>0.05)。CoCl2缺氧干预后加入BDNF干预各组(24h、48h、72h)与缺氧对照组及正常对照组相比,Muller细胞对谷氨酸的摄取量增加(P<0.05),以CoCl2缺氧干预72h,BDNF干预48h组谷氨酸的摄取量最大(P<0.05)。加入CoCl2溶液及BDNF干预后,Muller细胞死亡数较正常对照组无明显差异(P>0.05)。
结论BDNF能够上调缺氧状态下视网膜Muller细胞GLAST及GS的表达,并增加Muller细胞对细胞外谷氨酸的摄取。
Chapterl Effect of BDNF on the GLAST and GS in mouse retinal Miiller cells under normal oxygen condition
Objective:To study the effect of brain-derived neurotrophic factor (BDNF) on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Miiller cells (RMCs) under normal oxygen conditions.
Methods:Retinal Miiller cells (RMCs) of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs passaged three times were used in next experiments. RMCs cultures were divided into BDNF group:Cultured retinal Muller cells were maintained with different concentrations of recombinant human BDNF (50ng/ml,75ng/ml,100ng/ml,125ng/ml or150ng/ml)for24h in vitro, and Control group:Cultured retinal Muller cells were maintained without BDNF. The expression of GLAST and GS mRNA was measured by RT-PCR. The expression of GLAST and GS protein was measured by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs in BDNF group (100ng/ml) and normal control group.
Results:Different concentrations of BDNF could up-regulate GLAST and GS expression compared to normal control (p<0.05). The expression of GLAST and GS reached the maximum when the concentration of BDNF was100ng/ml. Immunocytochemistry demonstra-ted that GLAST was predominantly found in the membrane and cytoplasm, while GS was predominantly found in the cytoplasm. Both GLAST and GS immunostaining appeared more intense in BDNF-treated cells. L-[3,4-3H]-glutamic acid uptake of BDNF group (100ng/ml) was significantly higher than normal control group.
Conclusion:BDNF may up-regulate GLAST and GS expression to increase extracellular glutamate uptake under normal oxygen conditions.
Chapter2Effect of hypoxia on the GLAST and GS in mouse retinal Muller cells
Objective:This study investigated the effect of hypoxia on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Muller cells (RMCs)
Methods:RMCs of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs cultures were treated with CoCl2(125μmol/L) for6h,12h,24h,48h or72h respectively in vitro. RMCs cultures were maintained without CoCl2in normal control group. The expression of GLAST and GS mRNA was determined by RT-PCR. The expression of GLAST and GS protein was determined by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs. The apoptosis of RMCs was confirmed by annexin V-FITC/PI staining.
Results:In early-stage of CoCl2-induced hypoxia (treated with CoCl2for6h,12h,24h or48h), the expression of GLAST was up-regulated (p<0.001) and reached the maximum when RMCs have been treated with CoCl2for12h (p<0.05). After RMCs have been treated with CoCl2for72h, the expression of GLAST had no difference compared to normal control (p>0.05). CoCl2-induced hypoxia (treated with CoCl2for6h,12h,24h,48h or72h) also up-regulated the expression of GS (p<0.001), which reached the maximum when RMCs have been treated with CoCl2for48h (p<0.001). The L-[3,4-3H]-glutamic acid uptake of hypoxia groups were higher than normal control group (p<0.05), and after having treated RMCs with CoCl2for48h, the L-[3,4-3H]-glutamic acid uptake was highest (p<0.005). Treatments with CoCl2did not induce apoptosis in RMCs.
Conclusion:In early hypoxia stage, GLAST and GS may be up-regulated and extracellular glutamate uptake may be increased. However, continued hypoxia may cause gradual dysfunction and decreasing of GLAST and GS expression, as well as glutamate uptake.
Chapter3Effect of BDNF on the GLAST and GS in mouse retinal Miiller cells under hypoxia
Objective:To study the effect of brain-derived neurotrophic factor (BDNF) on the expression and function of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) in mouse retinal Miiller cells (RMCs) under hypoxia.
Method:RMCs of Kunming mouse at postnatal3to7days were cultured by enzymatic digestion. RMCs cultures were treated with CoCl2(125μmol/L) for72h, then combined with BDNF (100ng/ml) for24,48,72, or96h. RMCs cultures were maintained without CoCl2and BDNF in normal controls, RMCs cultures were maintained with CoCl2for72h in hypoxia controls. The expression of GLAST and GS mRNA was determined by RT-PCR. The expression of GLAST and GS protein was determined by western blotting and immunocytochemical staining. L-[3,4-3H]-glutamic acid uptake was used to quantify glutamate uptake function of RMCs. The apoptosis of RMCs was confirmed by annexin V-FITC/PI staining.
Result:BDNF treatment increased GLAST and GS mRNA and protein levels compared to nomal controls (p<0.001) and to hypoxia controls (p<0.05). Maximum protection was observed at48h after BDNF treatment (p<0.05), However, when BDNF treatment occurred at24h before CoCl2treatment, GLAST and GS expression had no difference compared to normal controls (p>0.05). Both GLAST and GS immunostaining appeared more intense when BDNF treatment occurred after CoCl2treatment, but not when BDNF treatment occurred at24h before CoCl2treatment. At72h after hypoxia, BDNF treatment also increased L-[3,4-3H]-glutamic acid uptake compared to nomal controls (p <0.001) and hypoxia controls (p<0.005), and this effect was maximal at48h after BNDF treatment. Hypoxia combined with BNDF had not induce death (apoptotic and necrotic) of RMCs compared with controls (p>0.05).
Conclusion:BDNF may up-regulate GLAST and GS expression and increase extracellular glutamate uptake in RMCs under hypoxia, but BDNF treatment has no effect at24h before hypoxia.
引文
[1]Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron,1988,1:623-634.
[2]Newman E, Reichenbach A. The Miiller cell:a functional element of the retina. Trends Neurosci,1996,19:307-312.
[3]Napper G, Pianta M, Kalloniatis M. Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci,1999,16:149-158.
[4]Carter-Dawson L, Shen F, Harwerth R, et al. Glutamine immunoreactivity in Muller cells of monkey eyes with experimental glaucoma. Exp Eye Res,1998, 66:537-545.
[5]Munir M, Correale DM, Robinson MB. Substrate-induced upregulation of Na(+)-dependent glutamate transport activity. Neurochem Int,2000,37: 147-162.
[6]Brandstatter JH, Hartveit E, Sassoe-Pognetto M, et al. Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur J Neurosci,1994,6:1100-1112.
[7]Eliasof S, Arriza JL, Leighton BH, et al. Excitatory amino acid transporters of the salamander retina:identification, localization and function. J Neurosci, 1998,18:698-712.
[8]Rauen T, Rothstein JD, Wassle H. Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res,1996,286:325-336.
[9]Rauen T, Taylor WR, Kuhlbrodt K, et al. High-affinity glutamate transporters in the rat retina:a major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell Tissue Res,1998,291:19-31.
[10]Barnett NL, Pow DV, Bull ND, et al. Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia. Neurochem Int,2001, 39:291-299.
[11]Danbolt NC. Glutamate uptake. Prog Neurobiol,2001,65:1-105.
[12]Atsusbi K, Yasumasa O, Colin JB. Muller cell protection of rat retinal ganglion cells from glutamate and nitric oxide eurotoxicity. Invest Ophthal mol Vis Sci,2000,41:3444-3450.
[13]Cohen-Cory S, Escandon E, Fraser SE. The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF during Xenopus visual system development. Dev Biol,1996,179:102-115.
[14]Ma Y-T, Hsieh T, Forbes ME, et al. BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death. J Neurosci,1998,18: 2097-2107.
[15]Castillo B Jr, del Cerro M, Breakefield XO, et al. Retinal ganglion cell survival is promoted by genetically modified astrocytes designed to secrete brain-derived neurotrophic factor (BDNF). Brain Res.1994,647:30-36.
[16]Ko ML, Hu DN, Ritch R, et al. The combined effect of brain-derived neurotrophic factor and a free radical scavenger in experimental glaucoma. Invest Ophthalmol Vis Sci,2000,41:2967-2971.
[17]Pernet V, Di Polo A. Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo. Brain 2006,129:1014-1026.
[18]Watanabe M, Tokita Y, Kato M, et al. Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized beta ganglion cells in cat retina. Neuroscience,2003,116:733-742.
[19]Di Polo A, Aigner LJ, Dunn RJ, et al. Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells. Proc Natl Acad Sci USA,1998,95:3978-3983.
[20]Martin KR, Quigley HA, Zack DJ, et al. Gene therapy with brain-derived neurotrophic factor as a protection:retinal ganglion cells in a rat model of glaucoma. Invest Ophthalmol Vis Sci,2003,44:4357-4365.
[21]黄正如,管怀进.BDNF对实验性急性高眼压兔眼视网膜神经节细胞的保护作用.苏州大学学报(医学版)2005,25：800-802.
[22]王芳,赛因·贺西格,于振珏等.大鼠Muller细胞的体外培养及免疫组织化学鉴定.解剖学杂志,2005,28：599-601.
[23]Bringmann A, Pannicke T, Grosche J, et al. Muller cells in the healthy and diseased retina. Prog Retin Eye Res,2006,25:397-424.
[24]Barde YA, Edgar D, Thoenen H, et al. Purification of a new neurotrophic factor from mammalian brain. EMBO J,1982,1:549-553.
[25]Herzog KH, Von Bartheld CS. Contributions of the optic tectum and the retina as sources of brain-derived neurotrophic factor for retinal ganglion cells in the chick embryo. J Neurosci,1998,18:2891-2906.
[26]Ota T, Hara H, Miyawaki N. Brain-derived neurotrophic factor inhibits changes in soma-size of retinal ganglion cells following optic nerve axotomy in rats. J Ocul Pharmacol Ther,2002,18:241-249.
[27]Lewis GP, Linberg KA, Geller SF, et al. Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci,1999,40:1530-1544.
[28]Castren E, Zafra F, Thoenen H, et al. Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci USA,1992,89:9444-9448.
[29]Harada T, Harada C, Kohsaka S, et al. Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. J Neurosci, 2002,22:9228-9236.
[30]陈蓉.脑源性神经营养因子对体外培养的海马神经细胞的作用研究.湛江师范学院学报(自然科学版),1997,18：69-71.
[31]Chen H, Weber AJ. BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci,2001,42:966-974.
[32]Klocker N, Kermer P, Gleichmann M, et al. Both the neuronal and inducible isoforms contribute to upregulation of retinal nitric oxide synthase activity by brain-derived neurotrophic factor. J Neurosci,1999,19:8517-8527.
[33]Weinreb RN, Levin LA. Is neuroprotection a viable therapy for glaucoma? Arch Ophthalmol,1999,117:1540-1544.
[34]Rocha M, Martins RA, Linden R. Activation of NMDA receptors protects against glutamate neurotoxicity in the retina:evidence for the involvement of neurotrophins. Brain Res,1999,827:79-92.
[35]Taylor S, Srinivasan B, Wordinger RJ, et al. Glutamate stimulates neurotrophin expression in cultured Muller cells. Mol Brain Res,2003,111: 189-197.
[36]Delyfer MN, Forster V, Neveux N, et al. Evidence for glutamate-mediated excitotoxic mechanisms during photo receptor degeneration in the rdl mouse retina. Mol Vis,2005,11:688-696.
[37]熊鲲,黄菊芳,潘爱华等.急性眼高压大鼠视网膜谷氨酸／天冬氨酸转运体和谷氨酰胺合成酶的表达.解剖学杂志,2005,26：308-310.
[38]Naskar R, Vorwerk CK, Dreyer EB. Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci,2000,41: 1940-1944.
[39]Kobayashi S, Millhorn DE. Hypoxia regulates glutamate metabolism and membrane transport in rat PC12 cells. J Neurochem,2001,76:1935-1948.
[40]Dallas M, Boycott HE, Atkinson L, et al. Hypoxia suppresses glutamate transport in astrocytes. J Neurosci,2007,27:3946-3955.
[41]Liu FQ, Liu Y, Lui VC, et al. Hypoxia modulates lipopolysaccharide induced TNF-a expression in murine macrophages. Exp Cell Res,2008,314: 1327-1336.
[42]Shirato K, Kizaki T, Sakurai T. et al. Hypoxia-inducible factor-1 alpha suppresses the expression of macrophage scavenger receptor 1. Pflugers Arch, 2009,459:93-103.
[43]Bringmann A, Pannicke T, Biedermann B, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int,2009,54:143-160.
[44]Delyfer MN, Simonutti M, Neveux N, et al. Does GDNF exert its neuroprotective effects on photoreceptors in the rdl retina through the glial glutamate transporter GLAST? Mol Vis,2005,11:677-687.
[45]Harper MM, Adamson L, Blits B, et al. Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate-and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells. Exp Eye Res.2009,89:538-548.
[46]Ikeda K, Tanihara H, Honda Y, et al. BDNF attenuates retinal cell death caused by chemically induced hypoxia in rats. Invest Ophthalmol Vis Sci,1999,40: 2130-2140.
[47]Krueger-Naug AM, Emsley JG, Myers TL, et al. Administration of brain-derived neurotrophic factor suppresses the expression of heat shock protein 27 in rat retinal ganglion cells following axotomy. Neurosci,2003,116: 49-58.
[1]Hollander H, Makarov F, Dreher Z, et al. Structure of the macroglia of the retina:sharing and division of labour between astrocytes and Miiller cells.J Comp Neurol,1991,22:587-603.
[2]Reichenbach A, Stolzenburg JU, Eberhardt W, et al. What do retinal muller (glial) cells do for their neuronal 'small siblings'? J Chem Neuroanat,1993,6: 201-213.
[3]Newman E, Reichenbach A. The Muller cell:a functional element of the retina. Trends Neurosci,1996,19:307-312.
[4]Beretta S, Wood JP, Derham B, et al. Partial mitochondrial complex Ⅰ inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON). Neurobiol Dis,2006,24:308-317.
[5]Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons. J Neurosci,1996,16:877-885.
[6]Bringmann A, Reichenbach A, Wiedemann P. Pathomechanisms of cystoid macular edema. Ophthalmic Res,2004,36:241-249.
[7]Tout S, Chan-Ling T, Hollander H, et al. The role of Muller cells in the formation of the blood-retinal barrier. Neuroscience,1993,55:291-301.
[8]Choi YK, Kim KW. Blood-neural barrier:its diversity and coordinated cell-to-cell communication. BMB Rep,2008,41:345-352.
[9]Metea MR, Newman EA. Glial cells dilate and constrict blood vessels:a mechanism of neurovascular coupling. J Neurosci,2006,26:2862-2870.
[10]Newman EA. Glial modulation of synaptic transmission in the retina. Glia, 2004,47:268-274.
[11]Thoreson WB, Witkovsky P. Glutamate receptors and circuits in the vertebrate retina. Prog Retin Eye Res,1999,18:765-810.
[12]Massey SC, Miller RE N-methyl-D-aspartate receptors of ganglion cells in rabbit retina. J Neurophysiol,1990,63:16-30.
[13]Rauen T, Wiessner M. Fine tuning of glutamate uptake and degradation in glial cells:common transcriptional regulation of GLAST1 and GS. Neurochem Int, 2000,37:179-189.
[14]Beart PM, O'Shea RD. Transporters for L-glutamate:an update on their molecular pharmacology and pathological involvement. Br J Pharmacol,2007, 150:5-17.
[15]Rauen T. Diversity of glutamate transporter expression and function in the mammalian retina. Amino Acids,2000,19:53-62.
[16]Harada T, Harada C, Watanabe M, et al. Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc Natl Acad Sci U S A,1998, 95:4663-4666.
[17]Holcombe DJ, Lengefeld N, Gole GA, et al. The effects of acute intraocular pressure elevation on rat retinal glutamate transport. Acta Ophthalmol,2008, 86:408-414.
[18]Barnett NL, Pow DV, Bull ND. Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia. Neurochem Int,2001,39: 291-299.
[19]Rauen T, Rothstein JD, Wassle H. Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res,1996,286:325-336.
[20]Wadiche JI, Arriza JL, Amara SG, et al. Kinetics of a human glutamate transporter. Neuron,1995,14:1019-1027.
[21]Hasegawa J, Obara T, Tanaka K, et al. High-density presynaptic transporters are required for glutamate removal from the first visual synapse. Neuron,2006, 50:63-74.
[22]Matsui K, Hosoi N, Tachibana M. Active role of glutamate uptake in the synaptic transmission from retinal nonspiking neurons. J Neurosci,1999,19: 6755-6766.
[23]Higgs MH, Lukasiewicz PD. Glutamate uptake limits synaptic excitation of retinal ganglion cells. J Neurosci,1999,19:3691-3700.
[24]Vandenbranden CA, Verweij J, Kamermans M, et al. Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina. Vision Res, 1996,36:3859-3874.
[25]Copenhagen DR, Ashmore JF, Schnapf JK. Kinetics of synaptic transmission from photoreceptors to horizontal and bipolar cells in turtle retina. Vision Res, 1983,23:363-369.
[26]Sarantis M, Mobbs P. The spatial relationship between Muller cell processes and the photoreceptor output synapse. Brain Res,1992,584:299-304.
[27]Gebhard R. Cytochemical demonstration of aspartate aminotransferase activity in the rat retina. Brain Res,1991,539:337-341.
[28]Gebhard R. Histochemical demonstration of glutamate dehydrogenase and phosphate-activated glutaminase activities in semithin sections of the rat retina. Histochemistry,1992,97:101-103.
[29]Riepe RE, Norenburg MD. Muller cell localisation of glutamine synthetase in rat retina. Nature,1977,268:654-655.
[30]Pow DV, Robinson SR. Glutamate in some retinal neurons is derived solely from glia. Neuroscience,1994,60:355-366.
[31]Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron,1988,1:623-634.
[32]Kashii S, Mandai M, Kikuchi M, et al. Dual actions of nitric oxide in N-methyl-D-aspartate receptor-mediated neurotoxicity in cultured retinal neurons. Brain Res,1996,711:93-101.
[33]Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1:molecular, physiological and pharmacological aspects. Pflugers Arch, 2004,447:469-479.
[34]Derouiche A, Rauen T. Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance. J Neurosci Res,1995,42:131-143.
[35]Bouvier M, Miller BA, Szatkowski M, et al. lectrogenic uptake of sulphur-containing analogues of glutamate and aspartate by Miiller cells from the salamander retina. J Physiol,1991,444:441-457.
[36]Sarthy VP, Pignataro L, Pannicke T, et al. Glutamate transport by retinal Muller cells in glutamate/aspartate transporter-knockout mice. Glia,2005,49: 184-196.
[37]Macnab LT, Williams SM, Pow DV. Expression of the exon 3 skipping form of GLAST, GLASTla, in brain and retina. Neuroreport,2006,17:1867-1870.
[38]Macnab LT, Pow DV. Central nervous system expression of the exon 9 skipping form of the glutamate transporter GLAST. Neuroreport,2007,18: 741-745.
[39]Kugler P, Beyer A. Expression of glutamate transporters in human and rat retina and rat optic nerve. Histochem Cell Biol,2003,120:199-212.
[40]Fyk-Kolodziej B, Qin P, Dzhagaryan A, et al. Differential cellular and subcellular distribution of glutamate transporters in the cat retina. Vis Neurosci, 2004,21:551-565.
[41]Ward MM, Jobling AI, Kalloniatis M, et al. Glutamate uptake in retinal glial cells during diabetes. Diabetologia,2005,48:351-360.
[42]Eliasof S, Arriza JL, Leighton BH, et al. Excitatory amino acid transporters of the salamander retina:identification, localization, and function. J Neurosci, 1998,18:698-712.
[43]Barnett NL, Pow DV. Antisense knockdown of GLAST, a glial glutamate transporter, compromises retinal function. Invest Ophthalmol Vis Sci,2000,41: 585-591.
[44]Sarthy VP, Marc RE, Pignataro L, et al. Contribution of a glial glutamate transporter to GAB A synthesis in the retina. Neuroreport,2004,15: 1895-1898.
[45]Sullivan RK, Woldemussie E, Macnab L, et al. Evoked expression of the glutamate transporter GLT-lc in retinal ganglion cells in human glaucoma and in a rat model. Invest Ophthalmol Vis Sci,2006,47:3853-3859.
[46]Wersinger E, Schwab Y, Sahel JA, et al. The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells. J Physiol,2006, 577:221-234.
[47]Beart PM, O'Shea RD. Transporters for L-glutamate:an update on their molecular pharmacology and pathological involvement. Br J Pharmacol,2007, 150:5-17.
[48]Barbour B, Magnus C, Szatkowski M, et al. Changes in NAD(P)H fluorescence and membrane current produced by glutamate uptake into salamander Muller cells. J Physiol,1993,466:573-597.
[49]Grewer C, Rauen T. Electrogenic glutamate transporters in the CNS: molecular mechanism, pre-steady-state kinetics, and their impact on synaptic signaling. J Membr Biol,2005,203:1-220.
[50]Amato A, Barbour B, Szatkowski M, et al. Counter-transport of potassium by the glutamate uptake carrier in glial cells isolated from the tiger salamander retina. J Physiol,1994,479:371-380.
[51]Marcaggi P, Hirji N, Attwell D. Release of L-aspartate by reversal of glutamate transporters. Neuropharmacology,2005,49:843-849.
[52]Taylor S, Srinivasan B, Wordinger RJ, et al. Glutamate stimulates neurotrophin expression in cultured Muller cells. Mol Brain Res,2003,111: 189-197.
[53]Bull ND, Barnett NL. Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ. J Neurochem,2002,81:472-480.
[54]Sakai T, Yoshitoshi T, Nagai Y, et al. Increased glutamate uptake and GLAST expression by cyclic AMP in retinal glial cells. Graefes Arch Clin Exp Ophthalmol,2006,244:359-363.
[55]Naskar R, Vorwerk CK, Dreyer EB. Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci,2000,41: 1940-1944.
[56]Martin KR, Quigley HA, Zack DJ, et al. Gene therapy with brain-derived neurotrophic factor as a protection:retinal ganglion cells in a rat model of glaucoma. Invest Ophthalmol Vis Sci,2003,44:4357-4365.
[57]Delyfer MN, Forster V, Neveux N, et al. Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rdl mouse retina. Mol Vis,2005,11:688-696.
[58]Li Q, Puro DG. Diabetes-induced dysfunction of the glutamate transporter in retinal Muller cells. Invest Ophthalmol Vis Sci,2002,43:3009-3016.
[59]Napper GA, Pianta MJ, Kalloniatis M. Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci,1999,16:149-58.
[60]Barnett NL, Pow DV, Robinson SR. Inhibition of Muller cell glutamine synthetase rapidly impairs the retinal response to light. Glia,2000,30:64-73.
[61]Bringmann A, Pannicke T, Biedermann B, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int,2009,54:143-160.
[62]Chen CT, Alyahya K, Gionfriddo JR, et al. Loss of glutamine synthetase immunoreactivity from the retina in canine primary glaucoma. Vet Ophthalmol, 2008,11:150-157.
[63]Chen H, Weber AJ. Expression of glial fibrillary acidic protein and glutamine synthetase by Muller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor. Glia,2002,38:115-125.
[2]Newman E, Reichenbach A. The Miiller cell:a functional element of the retina. Trends Neurosci,1996,19:307-312.
[3]Napper G, Pianta M, Kalloniatis M. Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci,1999,16:149-158.
[4]Carter-Dawson L, Shen F, Harwerth R, et al. Glutamine immunoreactivity in Muller cells of monkey eyes with experimental glaucoma. Exp Eye Res,1998, 66:537-545.
[5]Munir M, Correale DM, Robinson MB. Substrate-induced upregulation of Na(+)-dependent glutamate transport activity. Neurochem Int,2000,37: 147-162.
[6]Brandstatter JH, Hartveit E, Sassoe-Pognetto M, et al. Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur J Neurosci,1994,6:1100-1112.
[7]Eliasof S, Arriza JL, Leighton BH, et al. Excitatory amino acid transporters of the salamander retina:identification, localization and function. J Neurosci, 1998,18:698-712.
[8]Rauen T, Rothstein JD, Wassle H. Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res,1996,286:325-336.
[9]Rauen T, Taylor WR, Kuhlbrodt K, et al. High-affinity glutamate transporters in the rat retina:a major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell Tissue Res,1998,291:19-31.
[10]Barnett NL, Pow DV, Bull ND, et al. Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia. Neurochem Int,2001, 39:291-299.
[11]Danbolt NC. Glutamate uptake. Prog Neurobiol,2001,65:1-105.
[12]Atsusbi K, Yasumasa O, Colin JB. Muller cell protection of rat retinal ganglion cells from glutamate and nitric oxide eurotoxicity. Invest Ophthal mol Vis Sci,2000,41:3444-3450.
[13]Cohen-Cory S, Escandon E, Fraser SE. The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF during Xenopus visual system development. Dev Biol,1996,179:102-115.
[14]Ma Y-T, Hsieh T, Forbes ME, et al. BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death. J Neurosci,1998,18: 2097-2107.
[15]Castillo B Jr, del Cerro M, Breakefield XO, et al. Retinal ganglion cell survival is promoted by genetically modified astrocytes designed to secrete brain-derived neurotrophic factor (BDNF). Brain Res.1994,647:30-36.
[16]Ko ML, Hu DN, Ritch R, et al. The combined effect of brain-derived neurotrophic factor and a free radical scavenger in experimental glaucoma. Invest Ophthalmol Vis Sci,2000,41:2967-2971.
[17]Pernet V, Di Polo A. Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo. Brain 2006,129:1014-1026.
[18]Watanabe M, Tokita Y, Kato M, et al. Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized beta ganglion cells in cat retina. Neuroscience,2003,116:733-742.
[19]Di Polo A, Aigner LJ, Dunn RJ, et al. Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells. Proc Natl Acad Sci USA,1998,95:3978-3983.
[20]Martin KR, Quigley HA, Zack DJ, et al. Gene therapy with brain-derived neurotrophic factor as a protection:retinal ganglion cells in a rat model of glaucoma. Invest Ophthalmol Vis Sci,2003,44:4357-4365.
[21]黄正如,管怀进.BDNF对实验性急性高眼压兔眼视网膜神经节细胞的保护作用.苏州大学学报(医学版)2005,25：800-802.
[22]王芳,赛因·贺西格,于振珏等.大鼠Muller细胞的体外培养及免疫组织化学鉴定.解剖学杂志,2005,28：599-601.
[23]Bringmann A, Pannicke T, Grosche J, et al. Muller cells in the healthy and diseased retina. Prog Retin Eye Res,2006,25:397-424.
[24]Barde YA, Edgar D, Thoenen H, et al. Purification of a new neurotrophic factor from mammalian brain. EMBO J,1982,1:549-553.
[25]Herzog KH, Von Bartheld CS. Contributions of the optic tectum and the retina as sources of brain-derived neurotrophic factor for retinal ganglion cells in the chick embryo. J Neurosci,1998,18:2891-2906.
[26]Ota T, Hara H, Miyawaki N. Brain-derived neurotrophic factor inhibits changes in soma-size of retinal ganglion cells following optic nerve axotomy in rats. J Ocul Pharmacol Ther,2002,18:241-249.
[27]Lewis GP, Linberg KA, Geller SF, et al. Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci,1999,40:1530-1544.
[28]Castren E, Zafra F, Thoenen H, et al. Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. Proc Natl Acad Sci USA,1992,89:9444-9448.
[29]Harada T, Harada C, Kohsaka S, et al. Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. J Neurosci, 2002,22:9228-9236.
[30]陈蓉.脑源性神经营养因子对体外培养的海马神经细胞的作用研究.湛江师范学院学报(自然科学版),1997,18：69-71.
[31]Chen H, Weber AJ. BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci,2001,42:966-974.
[32]Klocker N, Kermer P, Gleichmann M, et al. Both the neuronal and inducible isoforms contribute to upregulation of retinal nitric oxide synthase activity by brain-derived neurotrophic factor. J Neurosci,1999,19:8517-8527.
[33]Weinreb RN, Levin LA. Is neuroprotection a viable therapy for glaucoma? Arch Ophthalmol,1999,117:1540-1544.
[34]Rocha M, Martins RA, Linden R. Activation of NMDA receptors protects against glutamate neurotoxicity in the retina:evidence for the involvement of neurotrophins. Brain Res,1999,827:79-92.
[35]Taylor S, Srinivasan B, Wordinger RJ, et al. Glutamate stimulates neurotrophin expression in cultured Muller cells. Mol Brain Res,2003,111: 189-197.
[36]Delyfer MN, Forster V, Neveux N, et al. Evidence for glutamate-mediated excitotoxic mechanisms during photo receptor degeneration in the rdl mouse retina. Mol Vis,2005,11:688-696.
[37]熊鲲,黄菊芳,潘爱华等.急性眼高压大鼠视网膜谷氨酸／天冬氨酸转运体和谷氨酰胺合成酶的表达.解剖学杂志,2005,26：308-310.
[38]Naskar R, Vorwerk CK, Dreyer EB. Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci,2000,41: 1940-1944.
[39]Kobayashi S, Millhorn DE. Hypoxia regulates glutamate metabolism and membrane transport in rat PC12 cells. J Neurochem,2001,76:1935-1948.
[40]Dallas M, Boycott HE, Atkinson L, et al. Hypoxia suppresses glutamate transport in astrocytes. J Neurosci,2007,27:3946-3955.
[41]Liu FQ, Liu Y, Lui VC, et al. Hypoxia modulates lipopolysaccharide induced TNF-a expression in murine macrophages. Exp Cell Res,2008,314: 1327-1336.
[42]Shirato K, Kizaki T, Sakurai T. et al. Hypoxia-inducible factor-1 alpha suppresses the expression of macrophage scavenger receptor 1. Pflugers Arch, 2009,459:93-103.
[43]Bringmann A, Pannicke T, Biedermann B, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int,2009,54:143-160.
[44]Delyfer MN, Simonutti M, Neveux N, et al. Does GDNF exert its neuroprotective effects on photoreceptors in the rdl retina through the glial glutamate transporter GLAST? Mol Vis,2005,11:677-687.
[45]Harper MM, Adamson L, Blits B, et al. Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate-and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells. Exp Eye Res.2009,89:538-548.
[46]Ikeda K, Tanihara H, Honda Y, et al. BDNF attenuates retinal cell death caused by chemically induced hypoxia in rats. Invest Ophthalmol Vis Sci,1999,40: 2130-2140.
[47]Krueger-Naug AM, Emsley JG, Myers TL, et al. Administration of brain-derived neurotrophic factor suppresses the expression of heat shock protein 27 in rat retinal ganglion cells following axotomy. Neurosci,2003,116: 49-58.
[1]Hollander H, Makarov F, Dreher Z, et al. Structure of the macroglia of the retina:sharing and division of labour between astrocytes and Miiller cells.J Comp Neurol,1991,22:587-603.
[2]Reichenbach A, Stolzenburg JU, Eberhardt W, et al. What do retinal muller (glial) cells do for their neuronal 'small siblings'? J Chem Neuroanat,1993,6: 201-213.
[3]Newman E, Reichenbach A. The Muller cell:a functional element of the retina. Trends Neurosci,1996,19:307-312.
[4]Beretta S, Wood JP, Derham B, et al. Partial mitochondrial complex Ⅰ inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Relevance to Leber Hereditary Optic Neuropathy (LHON). Neurobiol Dis,2006,24:308-317.
[5]Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons. J Neurosci,1996,16:877-885.
[6]Bringmann A, Reichenbach A, Wiedemann P. Pathomechanisms of cystoid macular edema. Ophthalmic Res,2004,36:241-249.
[7]Tout S, Chan-Ling T, Hollander H, et al. The role of Muller cells in the formation of the blood-retinal barrier. Neuroscience,1993,55:291-301.
[8]Choi YK, Kim KW. Blood-neural barrier:its diversity and coordinated cell-to-cell communication. BMB Rep,2008,41:345-352.
[9]Metea MR, Newman EA. Glial cells dilate and constrict blood vessels:a mechanism of neurovascular coupling. J Neurosci,2006,26:2862-2870.
[10]Newman EA. Glial modulation of synaptic transmission in the retina. Glia, 2004,47:268-274.
[11]Thoreson WB, Witkovsky P. Glutamate receptors and circuits in the vertebrate retina. Prog Retin Eye Res,1999,18:765-810.
[12]Massey SC, Miller RE N-methyl-D-aspartate receptors of ganglion cells in rabbit retina. J Neurophysiol,1990,63:16-30.
[13]Rauen T, Wiessner M. Fine tuning of glutamate uptake and degradation in glial cells:common transcriptional regulation of GLAST1 and GS. Neurochem Int, 2000,37:179-189.
[14]Beart PM, O'Shea RD. Transporters for L-glutamate:an update on their molecular pharmacology and pathological involvement. Br J Pharmacol,2007, 150:5-17.
[15]Rauen T. Diversity of glutamate transporter expression and function in the mammalian retina. Amino Acids,2000,19:53-62.
[16]Harada T, Harada C, Watanabe M, et al. Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc Natl Acad Sci U S A,1998, 95:4663-4666.
[17]Holcombe DJ, Lengefeld N, Gole GA, et al. The effects of acute intraocular pressure elevation on rat retinal glutamate transport. Acta Ophthalmol,2008, 86:408-414.
[18]Barnett NL, Pow DV, Bull ND. Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia. Neurochem Int,2001,39: 291-299.
[19]Rauen T, Rothstein JD, Wassle H. Differential expression of three glutamate transporter subtypes in the rat retina. Cell Tissue Res,1996,286:325-336.
[20]Wadiche JI, Arriza JL, Amara SG, et al. Kinetics of a human glutamate transporter. Neuron,1995,14:1019-1027.
[21]Hasegawa J, Obara T, Tanaka K, et al. High-density presynaptic transporters are required for glutamate removal from the first visual synapse. Neuron,2006, 50:63-74.
[22]Matsui K, Hosoi N, Tachibana M. Active role of glutamate uptake in the synaptic transmission from retinal nonspiking neurons. J Neurosci,1999,19: 6755-6766.
[23]Higgs MH, Lukasiewicz PD. Glutamate uptake limits synaptic excitation of retinal ganglion cells. J Neurosci,1999,19:3691-3700.
[24]Vandenbranden CA, Verweij J, Kamermans M, et al. Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina. Vision Res, 1996,36:3859-3874.
[25]Copenhagen DR, Ashmore JF, Schnapf JK. Kinetics of synaptic transmission from photoreceptors to horizontal and bipolar cells in turtle retina. Vision Res, 1983,23:363-369.
[26]Sarantis M, Mobbs P. The spatial relationship between Muller cell processes and the photoreceptor output synapse. Brain Res,1992,584:299-304.
[27]Gebhard R. Cytochemical demonstration of aspartate aminotransferase activity in the rat retina. Brain Res,1991,539:337-341.
[28]Gebhard R. Histochemical demonstration of glutamate dehydrogenase and phosphate-activated glutaminase activities in semithin sections of the rat retina. Histochemistry,1992,97:101-103.
[29]Riepe RE, Norenburg MD. Muller cell localisation of glutamine synthetase in rat retina. Nature,1977,268:654-655.
[30]Pow DV, Robinson SR. Glutamate in some retinal neurons is derived solely from glia. Neuroscience,1994,60:355-366.
[31]Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron,1988,1:623-634.
[32]Kashii S, Mandai M, Kikuchi M, et al. Dual actions of nitric oxide in N-methyl-D-aspartate receptor-mediated neurotoxicity in cultured retinal neurons. Brain Res,1996,711:93-101.
[33]Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1:molecular, physiological and pharmacological aspects. Pflugers Arch, 2004,447:469-479.
[34]Derouiche A, Rauen T. Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST and GS in transmitter clearance. J Neurosci Res,1995,42:131-143.
[35]Bouvier M, Miller BA, Szatkowski M, et al. lectrogenic uptake of sulphur-containing analogues of glutamate and aspartate by Miiller cells from the salamander retina. J Physiol,1991,444:441-457.
[36]Sarthy VP, Pignataro L, Pannicke T, et al. Glutamate transport by retinal Muller cells in glutamate/aspartate transporter-knockout mice. Glia,2005,49: 184-196.
[37]Macnab LT, Williams SM, Pow DV. Expression of the exon 3 skipping form of GLAST, GLASTla, in brain and retina. Neuroreport,2006,17:1867-1870.
[38]Macnab LT, Pow DV. Central nervous system expression of the exon 9 skipping form of the glutamate transporter GLAST. Neuroreport,2007,18: 741-745.
[39]Kugler P, Beyer A. Expression of glutamate transporters in human and rat retina and rat optic nerve. Histochem Cell Biol,2003,120:199-212.
[40]Fyk-Kolodziej B, Qin P, Dzhagaryan A, et al. Differential cellular and subcellular distribution of glutamate transporters in the cat retina. Vis Neurosci, 2004,21:551-565.
[41]Ward MM, Jobling AI, Kalloniatis M, et al. Glutamate uptake in retinal glial cells during diabetes. Diabetologia,2005,48:351-360.
[42]Eliasof S, Arriza JL, Leighton BH, et al. Excitatory amino acid transporters of the salamander retina:identification, localization, and function. J Neurosci, 1998,18:698-712.
[43]Barnett NL, Pow DV. Antisense knockdown of GLAST, a glial glutamate transporter, compromises retinal function. Invest Ophthalmol Vis Sci,2000,41: 585-591.
[44]Sarthy VP, Marc RE, Pignataro L, et al. Contribution of a glial glutamate transporter to GAB A synthesis in the retina. Neuroreport,2004,15: 1895-1898.
[45]Sullivan RK, Woldemussie E, Macnab L, et al. Evoked expression of the glutamate transporter GLT-lc in retinal ganglion cells in human glaucoma and in a rat model. Invest Ophthalmol Vis Sci,2006,47:3853-3859.
[46]Wersinger E, Schwab Y, Sahel JA, et al. The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells. J Physiol,2006, 577:221-234.
[47]Beart PM, O'Shea RD. Transporters for L-glutamate:an update on their molecular pharmacology and pathological involvement. Br J Pharmacol,2007, 150:5-17.
[48]Barbour B, Magnus C, Szatkowski M, et al. Changes in NAD(P)H fluorescence and membrane current produced by glutamate uptake into salamander Muller cells. J Physiol,1993,466:573-597.
[49]Grewer C, Rauen T. Electrogenic glutamate transporters in the CNS: molecular mechanism, pre-steady-state kinetics, and their impact on synaptic signaling. J Membr Biol,2005,203:1-220.
[50]Amato A, Barbour B, Szatkowski M, et al. Counter-transport of potassium by the glutamate uptake carrier in glial cells isolated from the tiger salamander retina. J Physiol,1994,479:371-380.
[51]Marcaggi P, Hirji N, Attwell D. Release of L-aspartate by reversal of glutamate transporters. Neuropharmacology,2005,49:843-849.
[52]Taylor S, Srinivasan B, Wordinger RJ, et al. Glutamate stimulates neurotrophin expression in cultured Muller cells. Mol Brain Res,2003,111: 189-197.
[53]Bull ND, Barnett NL. Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ. J Neurochem,2002,81:472-480.
[54]Sakai T, Yoshitoshi T, Nagai Y, et al. Increased glutamate uptake and GLAST expression by cyclic AMP in retinal glial cells. Graefes Arch Clin Exp Ophthalmol,2006,244:359-363.
[55]Naskar R, Vorwerk CK, Dreyer EB. Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci,2000,41: 1940-1944.
[56]Martin KR, Quigley HA, Zack DJ, et al. Gene therapy with brain-derived neurotrophic factor as a protection:retinal ganglion cells in a rat model of glaucoma. Invest Ophthalmol Vis Sci,2003,44:4357-4365.
[57]Delyfer MN, Forster V, Neveux N, et al. Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rdl mouse retina. Mol Vis,2005,11:688-696.
[58]Li Q, Puro DG. Diabetes-induced dysfunction of the glutamate transporter in retinal Muller cells. Invest Ophthalmol Vis Sci,2002,43:3009-3016.
[59]Napper GA, Pianta MJ, Kalloniatis M. Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci,1999,16:149-58.
[60]Barnett NL, Pow DV, Robinson SR. Inhibition of Muller cell glutamine synthetase rapidly impairs the retinal response to light. Glia,2000,30:64-73.
[61]Bringmann A, Pannicke T, Biedermann B, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism. Neurochem Int,2009,54:143-160.
[62]Chen CT, Alyahya K, Gionfriddo JR, et al. Loss of glutamine synthetase immunoreactivity from the retina in canine primary glaucoma. Vet Ophthalmol, 2008,11:150-157.
[63]Chen H, Weber AJ. Expression of glial fibrillary acidic protein and glutamine synthetase by Muller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor. Glia,2002,38:115-125.