AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcle...AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.展开更多
Objective:To explore effect of retinal stem cells(RSCs)combined with copolymer-1(COP-1)immunotherapy on optic nerve damage in glaucoma rat model.Methods:A total of 40 SD rats were selected for glaucoma model and were ...Objective:To explore effect of retinal stem cells(RSCs)combined with copolymer-1(COP-1)immunotherapy on optic nerve damage in glaucoma rat model.Methods:A total of 40 SD rats were selected for glaucoma model and were randomly divided into 4 groups to observe protective effects of RSCs transplantation combined with COP-1.Results:Brain-derived neurotrophic factor(BDNF)and insulin like growth factor-1(IGF-1)were either positive in retina of RSCs transplanted or COP-1 immunological treated rat.Positive rate of BDNF and IGF-1 and expression of mRNA and protein were significantly higher in RSCs transplantation combined with COP-1immunotherapy treated rats compared with the other 3 groups,in which amount of apoptotic RGCs was lowest.Conclusions:RSCs transplantation combined with COP-1 immunotherapy can promote the secretion of BDNF and IGF-1.They protect RGCs in glaucoma rats in coordination,significantly reduce the number of apoptosis RGCs so as to alleviate the optic nerve damage.It ponits a new research direction for treatment of glaucoma.展开更多
目的:青光眼是一种多因素相关的视神经病变,致盲率高,其发病机制复杂,目前尚未明确。高眼压是目前唯一可调控的、与青光眼的发病密切相关的危险因素。本研究通过运用环角膜缘缝合与小梁网联合巩膜静脉激光光凝2种不同的方法建立慢性高...目的:青光眼是一种多因素相关的视神经病变,致盲率高,其发病机制复杂,目前尚未明确。高眼压是目前唯一可调控的、与青光眼的发病密切相关的危险因素。本研究通过运用环角膜缘缝合与小梁网联合巩膜静脉激光光凝2种不同的方法建立慢性高眼压大鼠模型,比较2种模型的眼压升高程度和高眼压持续时间,视网膜形态损伤和视网膜神经节细胞(retinal ganglion cells,RGCs)损伤程度,以及超微结构改变等。方法:建立2种慢性高眼压模型,分为环角膜缘缝合组(缝合组,用10/0尼龙线沿角巩膜缘缝合)和激光光凝组(激光组,激光灼烧小梁网联合巩膜外静脉),并以其对侧眼作为对照组。观察并定期规律监测2组大鼠的眼压变化。采用大鼠视网膜切片HE染色观察2种慢性高眼压模型对视网膜和视神经病理学的影响,透射电镜(transmission electron microscope,TEM)观察慢性高眼压模型超微结构中线粒体形态的变化,大鼠视网膜铺片Brn3b抗体免疫荧光染色特异性标记RGCs并计数,蛋白质印迹法检测凋亡相关蛋白caspase-3的表达以明确RGCs的凋亡情况。结果:与对照组相比,缝合组与激光组大鼠眼压均明显升高(均P<0.05),其中缝合组的眼压最高升高1.5倍,眼压显著升高持续8周;激光组的眼压最高达对照组的2倍,持续12周。2组都会导致RGCs丢失,与Brn3b染色的结果相符,2组caspase-3表达水平均升高(均P<0.05)。而在TEM下,2组RGCs中的线粒体形态均变为碎片化,从正常的长条形变小、变圆。与激光组相比,缝合组视网膜形态学的病理变化较轻微。结论:环角膜缘缝合可建立有效的慢性高眼压模型,诱导与激光光凝模型相似的青光眼性病理改变,但病理改变较激光光凝轻微。相较于激光光凝建模,环角膜缘缝合法对于设备要求和操作能力要求更低。展开更多
Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate ...Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.展开更多
Background Glaucoma,an irreversible optic nerve neuropathy,always results in blindness.This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization （EVC） model by multiple in vivo and...Background Glaucoma,an irreversible optic nerve neuropathy,always results in blindness.This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization （EVC） model by multiple in vivo and in vitro evidences.Methods Wistar rat was used in this study.The elevated intraocular pressure （IOP） was induced by cauterization of three episcleral veins.lOP was monitored with Tono-Pen XL tonometer.Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography.The function of retina was evaluated by electroretinogram （ERG）.Survival of retinal ganglion cells （RGCs） was quantified by retrograde labeling.Histology study was performed with retinal sections stained with hematoxylin-eosin,glial fibrillary acidic protein,and neuronal nuclear antigen.Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha （TNF-α） and alpha-2 macroglobulin （α2m） were measured with Western blotting.Results EVC is a relatively facile intervention,with low failure rates （＜5％）.After surgical intervention,chronic mild lOP elevation （about 1.6-fold over normal,P ＜0.05） was induced for at least 6 weeks without requiring a second intervention.High lOP causes chronic and progressive loss of RGCs （averaging about 4％ per week）,progressive thinning of neuronal retinal layers （3-5 μm per week）,and reduction of a-and b-wave in ERG.EVC method can also induce glial cell activation and alterations of inflammation proteins,such as TNF-α and α2m.Conclusion EVC method can establish a robust,reliable,economic and highly reproducible glaucomatous animal model.展开更多
目的:建立大鼠慢性高眼压模型,观察灯盏细辛(Erigeronbrevicapas hand mass,EBHM)对眼压升高诱导视神经损伤的保护作用。方法:选用健康成年Wistar大鼠90只,分为3组。用波长为532nm的氪离子黄绿激光光凝第1和第2组大鼠双眼小梁网,建立大...目的:建立大鼠慢性高眼压模型,观察灯盏细辛(Erigeronbrevicapas hand mass,EBHM)对眼压升高诱导视神经损伤的保护作用。方法:选用健康成年Wistar大鼠90只,分为3组。用波长为532nm的氪离子黄绿激光光凝第1和第2组大鼠双眼小梁网,建立大鼠高眼压模型。在眼压升高后1wk开始用EBHM对第2组大鼠15mg/100g肌肉注射,行视神经保护性治疗。第1组作为光凝对照组,第3组大鼠作为正常对照组。在第9wk同时处死3组大鼠做全视网膜铺片,1%甲苯氨蓝染色,记数平均视网膜神经节细胞(retinalganglion cells,RGCs)密度。结果:所有光凝眼眼压均中等程度升高,光凝前眼压为14.70±3.2mmHg;光凝后第3,6,9wk眼压分别为27.25±4.75,28.75±6.24,25.47±5.60mmHg,与光凝前比较,差别有显著性(P<0.05)。经视网膜铺片甲苯胺蓝染色,视网膜RGCs密度值(个/mm2)为:第1组1654±136,第2组2135±125,第3组2516±196。第2组大鼠视网膜RGCs密度值与第1和第3组大鼠RGCs密度值比较,差别有显著性(P<0.05)。结论:光凝大鼠小梁网成功建立大鼠慢性高眼压模型,光凝眼眼压中等程度升高,RGC密度降低;EBHM能够部分保护大鼠慢性高眼压诱导的视神经损害。展开更多
基金Supported by Gazi University Research and Education Fund
文摘AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.
基金supported by Shanghai Science and Technology Commission Project Fund(No 11ZR14121300)
文摘Objective:To explore effect of retinal stem cells(RSCs)combined with copolymer-1(COP-1)immunotherapy on optic nerve damage in glaucoma rat model.Methods:A total of 40 SD rats were selected for glaucoma model and were randomly divided into 4 groups to observe protective effects of RSCs transplantation combined with COP-1.Results:Brain-derived neurotrophic factor(BDNF)and insulin like growth factor-1(IGF-1)were either positive in retina of RSCs transplanted or COP-1 immunological treated rat.Positive rate of BDNF and IGF-1 and expression of mRNA and protein were significantly higher in RSCs transplantation combined with COP-1immunotherapy treated rats compared with the other 3 groups,in which amount of apoptotic RGCs was lowest.Conclusions:RSCs transplantation combined with COP-1 immunotherapy can promote the secretion of BDNF and IGF-1.They protect RGCs in glaucoma rats in coordination,significantly reduce the number of apoptosis RGCs so as to alleviate the optic nerve damage.It ponits a new research direction for treatment of glaucoma.
基金supported by the National Natural Science Foundation(81700838)the Natural Science Foundation of Hunan Province(2020JJ4789)the Scientific Research Project of Health Commission of Hunan Province(202307027224),China.
文摘目的:青光眼是一种多因素相关的视神经病变,致盲率高,其发病机制复杂,目前尚未明确。高眼压是目前唯一可调控的、与青光眼的发病密切相关的危险因素。本研究通过运用环角膜缘缝合与小梁网联合巩膜静脉激光光凝2种不同的方法建立慢性高眼压大鼠模型,比较2种模型的眼压升高程度和高眼压持续时间,视网膜形态损伤和视网膜神经节细胞(retinal ganglion cells,RGCs)损伤程度,以及超微结构改变等。方法:建立2种慢性高眼压模型,分为环角膜缘缝合组(缝合组,用10/0尼龙线沿角巩膜缘缝合)和激光光凝组(激光组,激光灼烧小梁网联合巩膜外静脉),并以其对侧眼作为对照组。观察并定期规律监测2组大鼠的眼压变化。采用大鼠视网膜切片HE染色观察2种慢性高眼压模型对视网膜和视神经病理学的影响,透射电镜(transmission electron microscope,TEM)观察慢性高眼压模型超微结构中线粒体形态的变化,大鼠视网膜铺片Brn3b抗体免疫荧光染色特异性标记RGCs并计数,蛋白质印迹法检测凋亡相关蛋白caspase-3的表达以明确RGCs的凋亡情况。结果:与对照组相比,缝合组与激光组大鼠眼压均明显升高(均P<0.05),其中缝合组的眼压最高升高1.5倍,眼压显著升高持续8周;激光组的眼压最高达对照组的2倍,持续12周。2组都会导致RGCs丢失,与Brn3b染色的结果相符,2组caspase-3表达水平均升高(均P<0.05)。而在TEM下,2组RGCs中的线粒体形态均变为碎片化,从正常的长条形变小、变圆。与激光组相比,缝合组视网膜形态学的病理变化较轻微。结论:环角膜缘缝合可建立有效的慢性高眼压模型,诱导与激光光凝模型相似的青光眼性病理改变,但病理改变较激光光凝轻微。相较于激光光凝建模,环角膜缘缝合法对于设备要求和操作能力要求更低。
基金supported by the National Natural Science Foundation of China,No.81570844the Natural Science Foundation of Fujian Province,No.2011D001+2 种基金Medical Innovation Program of Fujian Province,No.2011-CXB-47Huaxia Translational Medicine Youth Foundation,No.2017-A-00301Xiamen Science and Technology Program Guiding Project,No.3502Z20189033(all to RYW)。
文摘Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.
基金This work was supported by grants from Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme （2010）, Key Project of Guangdong Province Natural Science Foundation （No. 10251008901000028）.
文摘Background Glaucoma,an irreversible optic nerve neuropathy,always results in blindness.This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization （EVC） model by multiple in vivo and in vitro evidences.Methods Wistar rat was used in this study.The elevated intraocular pressure （IOP） was induced by cauterization of three episcleral veins.lOP was monitored with Tono-Pen XL tonometer.Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography.The function of retina was evaluated by electroretinogram （ERG）.Survival of retinal ganglion cells （RGCs） was quantified by retrograde labeling.Histology study was performed with retinal sections stained with hematoxylin-eosin,glial fibrillary acidic protein,and neuronal nuclear antigen.Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha （TNF-α） and alpha-2 macroglobulin （α2m） were measured with Western blotting.Results EVC is a relatively facile intervention,with low failure rates （＜5％）.After surgical intervention,chronic mild lOP elevation （about 1.6-fold over normal,P ＜0.05） was induced for at least 6 weeks without requiring a second intervention.High lOP causes chronic and progressive loss of RGCs （averaging about 4％ per week）,progressive thinning of neuronal retinal layers （3-5 μm per week）,and reduction of a-and b-wave in ERG.EVC method can also induce glial cell activation and alterations of inflammation proteins,such as TNF-α and α2m.Conclusion EVC method can establish a robust,reliable,economic and highly reproducible glaucomatous animal model.
文摘目的:建立大鼠慢性高眼压模型,观察灯盏细辛(Erigeronbrevicapas hand mass,EBHM)对眼压升高诱导视神经损伤的保护作用。方法:选用健康成年Wistar大鼠90只,分为3组。用波长为532nm的氪离子黄绿激光光凝第1和第2组大鼠双眼小梁网,建立大鼠高眼压模型。在眼压升高后1wk开始用EBHM对第2组大鼠15mg/100g肌肉注射,行视神经保护性治疗。第1组作为光凝对照组,第3组大鼠作为正常对照组。在第9wk同时处死3组大鼠做全视网膜铺片,1%甲苯氨蓝染色,记数平均视网膜神经节细胞(retinalganglion cells,RGCs)密度。结果:所有光凝眼眼压均中等程度升高,光凝前眼压为14.70±3.2mmHg;光凝后第3,6,9wk眼压分别为27.25±4.75,28.75±6.24,25.47±5.60mmHg,与光凝前比较,差别有显著性(P<0.05)。经视网膜铺片甲苯胺蓝染色,视网膜RGCs密度值(个/mm2)为:第1组1654±136,第2组2135±125,第3组2516±196。第2组大鼠视网膜RGCs密度值与第1和第3组大鼠RGCs密度值比较,差别有显著性(P<0.05)。结论:光凝大鼠小梁网成功建立大鼠慢性高眼压模型,光凝眼眼压中等程度升高,RGC密度降低;EBHM能够部分保护大鼠慢性高眼压诱导的视神经损害。
