Kuriyama H, Waki M, Nakagawa M, Tsuda M
Department of Life Science, Himeji Institute of Technology, Harima Science Garden City, Akoh-gun, Hyogo 678-1297, Japan.
Ophthalmic Res. 2001 Jul-Aug;33(4):196-202. doi: 10.1159/000055670.
Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 microM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.
评估了自由基清除剂CV - 3611对大鼠视网膜缺血损伤以及对细胞系中谷氨酸诱导的细胞毒性的保护作用。通过将大鼠眼压升高至110 mmHg持续45分钟诱导短暂性视网膜缺血，并测量视网膜电图（ERG）以评估视网膜功能。再灌注后立即无法记录到ERG，此后ERG逐渐恢复。在再灌注后长达24小时内，CV - 3611处理组（10 mg/kg，口服）的a波潜伏期以及a波和b波振幅的恢复明显优于对照组。在对照组和CV - 3611组中，再灌注后6小时内b波的恢复均优于a波，而在24小时再灌注后这种关系则相反。通过测量乳酸脱氢酶对谷氨酸（10 mM）诱导的N18 - RE - 105细胞（一种神经视网膜 - 神经母细胞瘤杂交瘤）的细胞毒性进行定量。3 microM和10 microM的CV - 3611显著减轻了谷氨酸诱导的N18 - RE - 105细胞的细胞毒性。因此，自由基清除剂（CV - 3611）促进了缺血再灌注损伤后视网膜功能的恢复，并改善了谷氨酸诱导的细胞毒性。这些结果表明氧自由基在视网膜缺血损伤的早期阶段起重要作用。此外，缺血后a波和b波的不同恢复过程表明，视网膜对缺血的选择性易损性在再灌注期间可能会在功能上发生变化。
