Nakazawa Toru, Shimura Masahiko, Tomita Hiroshi, Akiyama Hiroshi, Yoshioka Yuki, Kudou Hideyo, Tamai Makoto
Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan.
Curr Eye Res. 2003 Jan;26(1):55-63. doi: 10.1076/ceyr.26.1.55.14254.
The aim of this study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway can function as a neuroprotective pathway following induced retinal injury.
The activation of Akt was assessed by immunoblot analysis, and the role of PI3K/Akt pathway was evaluated by TUNEL staining and counting the number of retrogradely-labeled retinal ganglion cells (RGCs) in the whole retina at 168 h after injury with or without PI3K specific inhibitor, LY294002.
Akt was induced within one hr and reached a maximum 6 hrs after optic nerve clamping. The activation was observed in the RGC layer including RGCs, the inner plexiform layer, inner nuclear layer, and in the photoreceptor outer segments. The number of surviving RGCs was decreased significantly 168 hrs after injury. LY294002 partially inhibited the activation of Akt, and significantly decreased the number of surviving RGCs as compared with that of injury alone.
These results indicate that the PI3K/Akt signaling pathway is activated intrinsically and has a neuroprotective effect on injured RGCs.
本研究旨在确定磷脂酰肌醇3激酶（PI3K）/Akt信号通路在诱导性视网膜损伤后是否可作为一种神经保护通路发挥作用。
通过免疫印迹分析评估Akt的激活情况，并在损伤后168小时，使用或不使用PI3K特异性抑制剂LY294002，通过TUNEL染色和计数全视网膜中逆行标记的视网膜神经节细胞（RGC）数量来评估PI3K/Akt通路的作用。
视神经夹闭后1小时内诱导出Akt，6小时后达到最大值。在包括RGC的RGC层、内网状层、内核层以及光感受器外段均观察到激活。损伤后168小时存活的RGC数量显著减少。LY294002部分抑制了Akt的激活，与单纯损伤相比，显著降低了存活RGC的数量。
这些结果表明PI3K/Akt信号通路被内源性激活，对受损的RGC具有神经保护作用。
