Effect of glatiramer acetate on primary and secondary degeneration of retinal ganglion cells in the rat
Effect of glatiramer acetate on primary and secondary degeneration of retinal ganglion cells in the rat
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DOI：
10.1167/iovs.04-0731
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Quigley, H
中科院分区：
文献类型：
--
作者：
Blair, M;Pease, ME;Quigley, H
目的。在视神经挤压损伤、眼压升高和谷氨酸毒性后，免疫调节剂Glatiramer醋酸酯(GA，Cop-1；Copaxone；Teva制药工业，Pitach Tikva，以色列)已被证明可以减少视网膜神经节细胞(RGC)的延迟性细胞死亡。方法将131只Wistar大鼠分成10组，在双侧上丘立体定向注射荧光示踪剂(荧光金；荧光素，丹佛，CO)标记视网膜节细胞。他们同时接受(1)GA与完全弗氏佐剂(CIA)混合的皮下注射，(2)单独的CFA，或(3)生理盐水。1周后，将6个部分横断组动物的左侧视神经上1/3切断。另有4组患者行视神经全横断。部分切断后1周或4周、完全切断后1周或2周处死大鼠，取双眼视网膜。结果：在部分横切组中，在第1周和第4周，下部视网膜RGC丢失的平均百分比差异无统计学意义(ANOVA；P=0.20，P=0.12)。全视网膜切断后，GA组RGC丢失在1周时明显多于CIA组，但在2周时无统计学意义(双尾t检验，P=0.04，P=0.36)。结论：无论是对原发损伤还是继发累及RGC，均无证据表明GA对视神经切断后具有神经保护作用。
PURPOSE. After crush injury to the optic nerve, elevated intraocular pressure, and glutamate toxicity, the immune modulator glatiramer acetate (GA, Cop-1; Copaxone; Teva Pharmaceutical Industries, Pitach Tikva, Israel) has been shown to reduce the delayed cell death of retinal ganglion cells (RGCs). This study was undertaken to confirm the protective effect of GA on secondary degeneration of RGCs in the rat, by using a spatial, rather than temporal, model.METHODS. A total of 131 Wistar rats divided into 10 groups underwent bilateral stereotactic injection of fluorescent tracer (Fluorogold; Fluorochrome, Denver, CO) into the superior colliculus to label RGCs. They received a concurrent subcutaneously injection of (1) GA mixed with complete Freund's adjuvant (CIA), (2) CFA alone, or (3) saline. One week later, the superior one third of the left optic nerve was transected in animals in the six partial transection groups. Optic nerves in four additional groups underwent full transection. Rats were killed and retinas harvested from both eyes I or 4 weeks after partial transection and 1 or 2 weeks after full transection. RGC densities were calculated from retinal wholemounts, and differences between right (control) and left (transected) eyes were compared across treatment groups.RESULTS. Among the partial transection groups, differences in the mean percentage of RGC loss in the inferior retinas were not significant at I or 4 weeks (ANOVA; P = 0.20, P = 0.12, respectively). After full transection, there was significantly more RGC loss in the GA group than in the CIA group when comparing whole retinas at 1 week, but not at 2 weeks (two-tailed t-test; P = 0.04, P = 0.36, respectively).CONCLUSIONS. There is no evidence that GA has a neuroprotective effect after optic nerve transection, either for primarily injured or secondarily involved RGC.