干细胞移植对大鼠青光眼模型视神经保护作用及安全性的Meta分析

目的 系统评价干细胞移植对大鼠青光眼模型的视神经保护作用及其安全性。 方法 计算机检索PubMed、EMbase、The Cochrane Library、OVID、CBM、中国知网、维普和万方数据,搜集有关干细胞移植治疗青光眼的动物实验,检索时限均从建库起到2018年6月10日。由两名评价员独立的按照纳入和排除标准筛选文献、提取资料,采用SYRCLE动物实验偏倚风险评估表对纳入文献进行偏倚风险评价。采用RevMan 5.3软件进行统计分析。 结果 最终纳入8个研究,包括319只大鼠。Meta分析研究结果显示,实验组第28天的眼压低于对照组［SMD=-2.12,95%CI(-3.39,-0.85), Z=3.27,P=0.001］;实验组第14、28天视网膜神经节细胞计数高于对照组［SMD=4.51,95%CI(3.17,5.85), Z=6.60,P<0.00 001;SMD=2.96,95%CI(1.11,4.80), Z=3.14,P=0.002］;实验组第14天视网膜BDNF的表达高于对照组［SMD=2.67,95%CI(1.46,3.88), Z=4.32,P<0.0 001］;实验组第21、28天视网膜GDNF表达高于对照组［WMD=1.21,95%CI(1.05,1.37), Z=14.75,P<0.001;WMD=0.79,95%CI(0.52,1.06), Z=5.72,P<0.001］;实验组第14天视网膜IGF-I的表达高于对照组［SMD=4.31,95%CI(2.51,6.11), Z=4.69,P<0.001］;3项研究表明,干细胞可在眼内存活4周,少数可融入宿主视网膜,并表达神经细胞表面标志物;3项研究表明,干细胞眼内移植后无不良反应发生。 结论 现有证据显示,大鼠青光眼模型构建尚缺乏统一、规范的方法,干细胞移植对大鼠青光眼模型视神经有一定的保护作用,且安全性较高,但受纳入研究数量和质量的限制,上述结论还需更多高质量研究验证。

Neuroprotective effects and safety of stem cell transplantation in rats with experimental glaucoma: a systematic review

Objective To systematically review the neuroprotective effects and safety of transplanted stem cells in rats with experimental glaucoma. Methods Databases including PubMed, Embase, the Cochrane Library, Ovid, CBM, CNKI, VIP, and Wanfang Data were searched to collect information on animal experiments of stem cell transplantation for glaucoma, from inception to June 10, 2018. Two reviewers independently screened the literature in accordance with the inclusion and exclusion criteria, extracted the data, and assessed the risk of bias of the included studies using SYRCLE's risk of bias tool. Subsequently, a meta-analysis was performed using the RevMan 5.3 software. Results A total of 8 studies involving 319 rats were analyzed. The results of the meta-analysis showed that: 1)on the 28th day, the intraocular pressure was lower in the experimental group that in the control group ［SMD=-2.12, 95% CI:(-3.39, -0.85), Z=3.27, P=0.001］; 2)on the 14th day and the 28th day, the retinal ganglion cells were more in the experimental group than in the control group ［SMD=4.51, 95% CI:(3.17, 5.85), Z=6.60, P<0.001; SMD=2.96, 95% CI:(1.11, 4.80), Z=3.14, P=0.002］; 3)on the 14th day, the expression of BDNF was more in the retina of the experimental group than in the control group ［SMD=2.67, 95% CI:(1.46, 3.88), Z=4.32, P<0.001］; 4)on the 14th day and the 28th day, the expression of GDNF was more in the retina of the experimental group than in the control group ［WMD=1.21, 95% CI:(1.05, 1.37), Z=14.75, P<0.001; WMD=0.79, 95% CI:(0.52, 1.06), Z=5.72, P<0.001］; 5)on the 14th day, the expression of IGF-I was more in the retina of the experimental group than in the control group ［SMD=4.31, 95% CI:(2.51, 6.11), Z=4.69, P<0.001］. Three studies showed that stem cells could survive in the eye for 4 weeks and a few cells could integrate in the host retina and express neural cell surface markers. Three studies showed no adverse reactions after transplantation. Conclusions Although the current literature shows no uniform, standardized treatment method for experimental glaucoma in rats, there is evidence that stem cell transplantation has a certain protective effect on the optic nerve of rats with glaucoma, with no adverse reactions after transplantation. Because of the limited quality and quantity of the included literature, further studies are needed to validate the results of this review.