Otori Y, Shimada S, Morimura H, Ishimoto I, Tohyama M, Tano Y
Department of Ophthalmology, Osaka University Medical School, Japan.
Surv Ophthalmol. 1997 Nov;42 Suppl 1:S96-104. doi: 10.1016/s0039-6257(97)80032-x.
The expression of the proto-oncogenes c-fos and c-jun was examined by in situ hybridization at various timepoints following transient retinal ischemia by means of ligation of the retinal central artery in the rat. Ischemia of 90-minute duration resulted in the degeneration of neurons in both the ganglion cell layer and the inner nuclear layer at 48 hours after reperfusion. The expression of c-fos and c-jun messenger RNA throughout the entire inner nuclear layer was transiently coinduced following 90-minute retinal ischemia with a peak at 1 hour after reperfusion. This expression was also found in the ganglion cell layer at 3 hours after reperfusion. Weak signals for c-fos and c-jun mRNA were observed at 24 hours after reperfusion and returned to near control levels by 48 hours. c-jun protein expression was detected in the ganglion cell layer, the middle of the inner nuclear layer, and optic nerve head at 3 hours, but not 1 hour, after lethal ischemia/reperfusion; however, c-fos protein expression was not detected after reperfusion. Whereas no neuronal degenerative changes were found at 7 days after 30-minute ischemic retina, c-fos and c-jun messenger RNA were also induced at 1 hour postreperfusion. To our knowledge, this study is the first report to show expression patterns of immediate-early genes after retinal ischemia/reperfusion. These results suggest that changes in expression of c-fos and c-jun after transient retinal ischemia are similar to those after transient brain ischemia, and the selective occlusion of the central retinal artery will provide a useful model for studying ischemic neuronal degeneration in vivo in the rat retina.
通过结扎大鼠视网膜中央动脉造成短暂性视网膜缺血,在不同时间点采用原位杂交法检测原癌基因c-fos和c-jun的表达。持续90分钟的缺血导致再灌注后48小时神经节细胞层和内核层的神经元变性。90分钟视网膜缺血后,整个内核层c-fos和c-jun信使核糖核酸的表达被短暂共同诱导,在再灌注后1小时达到峰值。这种表达在再灌注后3小时的神经节细胞层中也有发现。再灌注后24小时观察到c-fos和c-jun信使核糖核酸的信号较弱,到48小时恢复到接近对照水平。在致死性缺血/再灌注后3小时而非1小时,在神经节细胞层、内核层中部和视神经乳头检测到c-jun蛋白表达;然而,再灌注后未检测到c-fos蛋白表达。30分钟缺血视网膜后7天未发现神经元退行性变化,但再灌注后1小时也诱导了c-fos和c-jun信使核糖核酸的表达。据我们所知,本研究是首次报道视网膜缺血/再灌注后即刻早期基因的表达模式。这些结果表明,短暂性视网膜缺血后c-fos和c-jun表达的变化与短暂性脑缺血后的变化相似,选择性闭塞视网膜中央动脉将为研究大鼠视网膜体内缺血性神经元变性提供一个有用的模型。