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
Objective To develop and evaluate the rat model of chronic glaucoma by episcleral veins ligation (EVL). Methods Experimental glaucoma was induced unilaterally in 28 male Sprague-Dawley rats by ligating two episclera...Objective To develop and evaluate the rat model of chronic glaucoma by episcleral veins ligation (EVL). Methods Experimental glaucoma was induced unilaterally in 28 male Sprague-Dawley rats by ligating two episcleral veins. Intraocular pressure (10P) in rats was measured by a Goldmann applanation tonometer under 3 % pentobarbital sodium anesthesia. The optic nerve head and retinal vasculature were assessed by repeated fundus examinations. The amount of optic nerve axons was assessed by Image-Pro Plus image analysis system in a masked fashion. Results lOP without EVL was ( 19.21 ± 1.23) mmHg, whereas the EVL eyes gained about 1.8-fold higher 10P[ (33.96 ±2. 73) mmHg]after EVL immediately ( P 〈 0. 001 ). The elevated IOP gradually decreased over time. However, the differences were kept significant up to 8 weeks after EVL. The lOP was reduced to similar levels as contralateral eyes at 12 and 16 weeks after EVL. The glaucomatous optic nerve excavation appeared in EVL eyes at 8 weeks after EVL, and the optic nerve excavation enlarged gradually with the increasing post-operation time. The amount of optic nerve axons also significantly decreased in EVL eyes at 8 weeks after EVL, and the amount of axons decreased gradually with the increasing post-operation time. Conclusion Increase of lOP caused by EVL represents a useful and efficient model of experimental glaucoma in rats.展开更多
AIM: To build a clinical diagnostic model of primary open angle glaucoma (POAG) using the normal probability chart of frequency-domain optical coherence tomography (FD-OCT). METHODS: This is a cross-sectional ...AIM: To build a clinical diagnostic model of primary open angle glaucoma (POAG) using the normal probability chart of frequency-domain optical coherence tomography (FD-OCT). METHODS: This is a cross-sectional study. Total 133 eyes from 133 healthy subjects and 99 eyes from 99 early POAG patients were included in the study. The retinal nerve fibre layer (RNFL) thickness parameters of optic nerve head (ONH) and RNFL3.45 scan were measured in one randomly selected eye of each subject using RTVue-100 FD-OCT. Then, we used these parameters to establish the diagnostic models. Four different diagnostic models based on two different area partition strategies on ONH and RNFL3.45 parameters, including ONH traditional area partition model (ONH-T), ONH new area partition model (ONH-N), RNFL3.45 traditional area partition model (RNFL3.45-T) and RNFL3.45 new area partition model (RNFL3.45-N), were built and tested by cross-validation. RESULTS: The new area partition models had higher area under the receiver operating characteristic (AROC; ONH-N: 0.990; RNFL3.45-N: 0.939) than corresponding traditional area partition models (ONH-T: 0.979; RNFL3.45-T: 0.881). There was no statistical difference among AROC of ONH-T, ONH-N, and RNFL3.45-N. Nevertheless, ONH-N was the simplest model. CONCLUSION: The new area partition models had higher diagnostic accuracy than corresponding traditional area partition models, which can improve the diagnostic ability of early POAG. In particular, the simplest ONH-N diagnostic model may be convenient for clinical application.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
AIM: To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid(NMDA) for intravitreal injection to establish a rat model of retinal neurodegeneration. METHODS: We injected different doses...AIM: To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid(NMDA) for intravitreal injection to establish a rat model of retinal neurodegeneration. METHODS: We injected different doses of glutamate(20 or 50 nmol) or NMDA(40 nmol) into the vitreous chambers of rats, then measured the concentration of glutamate and retinal thickness, quantified apoptotic cells and determined the degree of tau hyperphosphorylation at different time points. T-test was used for comparison of two groups. One-way ANOVA and Turkey's multiple comparisons test were used for comparisons of different groups, and P values below 0.05 were considered statistically significant.RESULTS: The glutamate level in the rats treated with 50 nmol of glutamate was twice that of the control group and persisted two weeks. Seven days after intravitreal injection of 50 nmol of glutamate, three parameters [inner retinal thickness(IRT), retinal thickness(RT) and ganglion cell layer(GCL) cell number] were reduced significantly. Furthermore, numerous TUNEL-positive cells were observed in the GCL one day after intravitreal injection of 50 nmol of glutamate, the expression of the apoptosisrelated factor cleaved casepase-3 was markedly increased compared with the expression levels in the other treatment groups, and the expression levels of tau s396 and tau s404 were significantly increased compared with those in the control group.CONCLUSION: This study demonstrates that the intravitreal injection of 50 nmol of glutamate can establish the more effective retinal neurodegeneration animal model relative to other treatment groups.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 Shanghai Education Committee Project Foundation (06BZ040)
文摘Objective To develop and evaluate the rat model of chronic glaucoma by episcleral veins ligation (EVL). Methods Experimental glaucoma was induced unilaterally in 28 male Sprague-Dawley rats by ligating two episcleral veins. Intraocular pressure (10P) in rats was measured by a Goldmann applanation tonometer under 3 % pentobarbital sodium anesthesia. The optic nerve head and retinal vasculature were assessed by repeated fundus examinations. The amount of optic nerve axons was assessed by Image-Pro Plus image analysis system in a masked fashion. Results lOP without EVL was ( 19.21 ± 1.23) mmHg, whereas the EVL eyes gained about 1.8-fold higher 10P[ (33.96 ±2. 73) mmHg]after EVL immediately ( P 〈 0. 001 ). The elevated IOP gradually decreased over time. However, the differences were kept significant up to 8 weeks after EVL. The lOP was reduced to similar levels as contralateral eyes at 12 and 16 weeks after EVL. The glaucomatous optic nerve excavation appeared in EVL eyes at 8 weeks after EVL, and the optic nerve excavation enlarged gradually with the increasing post-operation time. The amount of optic nerve axons also significantly decreased in EVL eyes at 8 weeks after EVL, and the amount of axons decreased gradually with the increasing post-operation time. Conclusion Increase of lOP caused by EVL represents a useful and efficient model of experimental glaucoma in rats.
文摘AIM: To build a clinical diagnostic model of primary open angle glaucoma (POAG) using the normal probability chart of frequency-domain optical coherence tomography (FD-OCT). METHODS: This is a cross-sectional study. Total 133 eyes from 133 healthy subjects and 99 eyes from 99 early POAG patients were included in the study. The retinal nerve fibre layer (RNFL) thickness parameters of optic nerve head (ONH) and RNFL3.45 scan were measured in one randomly selected eye of each subject using RTVue-100 FD-OCT. Then, we used these parameters to establish the diagnostic models. Four different diagnostic models based on two different area partition strategies on ONH and RNFL3.45 parameters, including ONH traditional area partition model (ONH-T), ONH new area partition model (ONH-N), RNFL3.45 traditional area partition model (RNFL3.45-T) and RNFL3.45 new area partition model (RNFL3.45-N), were built and tested by cross-validation. RESULTS: The new area partition models had higher area under the receiver operating characteristic (AROC; ONH-N: 0.990; RNFL3.45-N: 0.939) than corresponding traditional area partition models (ONH-T: 0.979; RNFL3.45-T: 0.881). There was no statistical difference among AROC of ONH-T, ONH-N, and RNFL3.45-N. Nevertheless, ONH-N was the simplest model. CONCLUSION: The new area partition models had higher diagnostic accuracy than corresponding traditional area partition models, which can improve the diagnostic ability of early POAG. In particular, the simplest ONH-N diagnostic model may be convenient for clinical application.
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 National Natural Science Foundation of China (No.81400398)
文摘AIM: To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid(NMDA) for intravitreal injection to establish a rat model of retinal neurodegeneration. METHODS: We injected different doses of glutamate(20 or 50 nmol) or NMDA(40 nmol) into the vitreous chambers of rats, then measured the concentration of glutamate and retinal thickness, quantified apoptotic cells and determined the degree of tau hyperphosphorylation at different time points. T-test was used for comparison of two groups. One-way ANOVA and Turkey's multiple comparisons test were used for comparisons of different groups, and P values below 0.05 were considered statistically significant.RESULTS: The glutamate level in the rats treated with 50 nmol of glutamate was twice that of the control group and persisted two weeks. Seven days after intravitreal injection of 50 nmol of glutamate, three parameters [inner retinal thickness(IRT), retinal thickness(RT) and ganglion cell layer(GCL) cell number] were reduced significantly. Furthermore, numerous TUNEL-positive cells were observed in the GCL one day after intravitreal injection of 50 nmol of glutamate, the expression of the apoptosisrelated factor cleaved casepase-3 was markedly increased compared with the expression levels in the other treatment groups, and the expression levels of tau s396 and tau s404 were significantly increased compared with those in the control group.CONCLUSION: This study demonstrates that the intravitreal injection of 50 nmol of glutamate can establish the more effective retinal neurodegeneration animal model relative to other treatment groups.