Li Lei, Chen Li-Ping, Liu Qing-Huai
Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Department of Ophthalmology, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, China.
Int J Ophthalmol. 2018 Feb 18;11(2):208-215. doi: 10.18240/ijo.2018.02.05. eCollection 2018.
To explore the effect of the Notch signaling pathway on retinal ganglion cells (RGCs) and optic nerve in rats with acute ocular hypertension (OH).
Totally 48 Sprague-Dawley (SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 µL phosphate buffered solution (PBS) and another group of OH rats received a single intravitreal injection of 10 µmol/L γ-secretase inhibitor (DAPT). Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43 (GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining.
The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBS-injected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.
The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.
探讨Notch信号通路对急性高眼压（OH）大鼠视网膜神经节细胞（RGCs）和视神经的影响。
共纳入48只Sprague-Dawley（SD）大鼠，其中36只大鼠被选来建立急性OH模型。OH大鼠接受单次玻璃体内注射2 μL磷酸盐缓冲溶液（PBS），另一组OH大鼠接受单次玻璃体内注射10 μmol/L γ-分泌酶抑制剂（DAPT）。采用定量实时聚合酶链反应（qPCR）和蛋白质免疫印迹法检测Notch的mRNA水平以及Notch、Bcl-2、Bax、caspase-3和生长相关蛋白43（GAP-43）的蛋白水平。通过TUNEL染色评估RGC凋亡情况。
与正常大鼠相比，OH大鼠和注射PBS的大鼠Notch1、Bax、caspase-3和GAP-43的表达水平升高，Bcl-2的表达水平降低，RGC凋亡增加，黄斑水肿更严重，RGC排列更松散。与OH大鼠和注射PBS的大鼠相比，DAPT处理的大鼠Notch1、Bax、caspase-3和GAP-43的表达水平升高，Bcl-2的表达水平降低，RGC凋亡增加。在DAPT处理的大鼠中几乎观察不到RGC，黄斑水肿变得严重。
Notch信号通路可能抑制急性OH大鼠视网膜神经节细胞的凋亡，并促进受损视神经的再生。
