Ophthalmology Department, First People's Hospital, an Affiliate of Shanghai Jiaotong University, Shanghai, China.
Curr Eye Res. 2011 Aug;36(8):739-46. doi: 10.3109/02713683.2011.582661.
To observe the effects of a single intravitreal rhEPO injection on light-induced retinal damage in rats and to explore the possible mechanisms.
Male Sprague-Dawley rats were randomly divided into a normal group, a control group (PBS intravitreal injection), and a number of treatment groups (intravitreal rhEPO injection at 0.625, 1.25, 2.5, 5, 10, or 20 U). After dark adaptation for 24 h, rats were exposed to white light (2800 lx) for 5 h. Based on the effects of rhEPO on the ERG-b wave, an optimal dose (5U) was chosen for further experiments that included histopathological examination and outer nuclear layer (ONL) counting at 5 and 10 days after light exposure. Cell apoptosis and proteins (caspase-3, bcl-xL) were also examined at 3 days. Some cell signaling related proteins (AKT, ERK1/2 and STAT5) were also analyzed. In another experiment, rats received intravitreal injection of rhEPO (5U) at 30 min after light exposure. ERG and morphological changes were examined at 3 days after light exposure.
ERG-b wave amplitudes are well preserved in rats receiving 2.5, 5, or 10 U rhEPO, in comparison with the PBS control. The dose-effect relationship was bell-shaped, with the maximum effect at 5 U. Less apoptotic cells were in the ONL in the 5U group. The rats receiving 5 U rhEPO at 30 min after light exposure also had higher b-wave amplitude. Caspase-3 expression was down-regulated and Bcl-xL was up-regulated in the rhEPO group. Phosphorylated ERK(1,2) was reduced in the rhEPO group.
A single intravitreal injection of rhEPO can postpone photoreceptor light damage in rats. The optimal dose was 5 U in this study. The effective time window was from 24 h prior to light exposure to 5 h after. RhEPO may be involved in the regulation of the expression of Caspase-3 and Bcl-xL. The possible cell signal transduction maybe through the ERK1/2 pathway.
观察单次玻璃体内重组人红细胞生成素（rhEPO）注射对大鼠光诱导视网膜损伤的影响，并探讨其可能的机制。
雄性 Sprague-Dawley 大鼠随机分为正常组、对照组（PBS 玻璃体内注射）和多个治疗组（0.625、1.25、2.5、5、10 或 20U 玻璃体内 rhEPO 注射）。暗适应 24h 后，大鼠暴露于白光（2800lx）5h。根据 rhEPO 对 ERG-b 波的影响，选择最佳剂量（5U）进行进一步实验，包括光暴露后 5 天和 10 天的组织病理学检查和外核层（ONL）计数。在 3 天还检查了细胞凋亡和蛋白（caspase-3、bcl-xL）。还分析了一些细胞信号相关蛋白（AKT、ERK1/2 和 STAT5）。在另一项实验中，大鼠在光暴露后 30min 接受玻璃体内 rhEPO（5U）注射。在光暴露后 3 天检查 ERG 和形态变化。
与 PBS 对照组相比，接受 2.5、5 或 10U rhEPO 的大鼠 ERG-b 波振幅保存良好。剂量效应关系呈钟形，最大效应在 5U。5U 组 ONL 中的凋亡细胞较少。在光暴露后 30min 接受 5U rhEPO 注射的大鼠 b 波振幅也较高。rhEPO 组 caspase-3 表达下调，Bcl-xL 上调。rhEPO 组磷酸化 ERK（1,2）减少。
单次玻璃体内注射 rhEPO 可延缓大鼠光感受器光损伤。在本研究中，最佳剂量为 5U。有效时间窗口为光暴露前 24h 至光暴露后 5h。rhEPO 可能参与调节 caspase-3 和 Bcl-xL 的表达。可能的细胞信号转导途径可能通过 ERK1/2 途径。
