Blair Michael, Pease Mary Ellen, Hammond John, Valenta Danielle, Kielczewski Jennifer, Levkovitch-Verbin Hana, Quigley Harry
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287, USA.
Invest Ophthalmol Vis Sci. 2005 Mar;46(3):884-90. doi: 10.1167/iovs.04-0731.
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.
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 (CFA), (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 1 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.
Among the partial transection groups, differences in the mean percentage of RGC loss in the inferior retinas were not significant at 1 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 CFA group when comparing whole retinas at 1 week, but not at 2 weeks (two-tailed t-test; P = 0.04, P = 0.36, respectively).
There is no evidence that GA has a neuroprotective effect after optic nerve transection, either for primarily injured or secondarily involved RGC.
在视神经挤压伤、眼压升高和谷氨酸毒性作用后，免疫调节剂醋酸格拉替雷（GA，Cop-1；Copaxone；梯瓦制药工业公司，以色列皮塔奇蒂克瓦）已被证明可减少视网膜神经节细胞（RGC）的延迟性细胞死亡。本研究旨在通过使用空间而非时间模型来证实GA对大鼠RGC继发性变性的保护作用。
将131只Wistar大鼠分为10组，对其双侧进行立体定向注射荧光示踪剂（Fluorogold；Fluorochrome，科罗拉多州丹佛市）至上丘，以标记RGC。它们同时接受皮下注射：（1）GA与完全弗氏佐剂（CFA）混合，（2）单独使用CFA，或（3）生理盐水。一周后，在六个部分横断组的动物中，切断左侧视神经上三分之一。另外四个组的视神经进行完全横断。在部分横断后1或4周以及完全横断后1或2周处死大鼠并摘取双眼视网膜。从视网膜全层标本计算RGC密度，并比较各治疗组右眼（对照）和左眼（横断）之间的差异。
在部分横断组中，1周或4周时下部视网膜RGC损失的平均百分比差异不显著（方差分析；P分别为0.20和0.12）。完全横断后，在1周时比较整个视网膜，GA组的RGC损失明显多于CFA组，但在2周时并非如此（双侧t检验；P分别为0.04和0.36）。
没有证据表明GA在视神经横断后对原发性损伤或继发性受累的RGC具有神经保护作用。
