Traumatic optic neuropathy (TON) is characterized by visual dysfunction after indirect or direct injury to the optic nerve following blunt head trauma. TON is associated with increased oxidative stress and inflammation resulting in retinal ganglion cell (RGC) death. Remote ischemic post-conditioning (RIC) has been shown to enhance endogenous protective mechanisms in diverse disease models including stroke, vascular cognitive impairment (VCI), retinal injury and optic nerve injury. However, the protective mechanisms underlying the improvement of retinal function and RGC survival after RIC treatment remain unclear. Here, we hypothesized that RIC therapy may be protective following TON by preventing RGC death, oxidative insult and inflammation in the mouse retina. To carry out the study, mice were divided in three different groups (Control, TON and TON + RIC). We harvested retinal tissue 5 days after TON induction for western blotting and histochemical analysis. We observed increased TON-induced retinal cell death compared with controls by cleaved caspase-3 immunohistochemistry. Furthermore, the TON cohort demonstrated increased TUNEL positive cells which were significantly attenuated by RIC. Immunofluorescence data showed that oxidative stress markers dihydroethidium (DHE), NOX-2 and nitrotyrosine expression were elevated in the TON group relative to controls and RIC therapy significantly reduced the expression level of these markers. Next, we found that the proinflammatory cytokine TNF-α was increased and anti-inflammatory IL-10 was decreased in plasma of TON animals, and RIC therapy reversed this expression level. Interestingly, western blotting of retinal tissue showed that RGC marker Brn3a and tight junction proteins (ZO-1 and Occludin), and AMPKα1 expression were downregulated in the TON group compared to controls. However, RIC significantly increased the expression levels of these proteins. Together these data suggest that RIC therapy activates endogenous protective mechanisms which may attenuate TON-induced oxidative stress and inflammation, and improves BRB integrity.

创伤性视神经病变 (TON) 的特征是在钝性头部外伤后对视神经造成间接或直接损伤后的视觉功能障碍。TON 与导致视网膜神经节细胞 (RGC) 死亡的氧化应激和炎症增加有关。远程缺血后处理 (RIC) 已被证明可增强多种疾病模型的内源性保护机制，包括中风、血管性认知障碍 (VCI)、视网膜损伤和视神经损伤。然而，RIC 治疗后视网膜功能改善和 RGC 存活的保护机制仍不清楚。在这里，我们假设 RIC 治疗可能通过预防小鼠视网膜中的 RGC 死亡、氧化损伤和炎症来保护 TON 后。为了进行这项研究，将小鼠分为三个不同的组（对照组，TON 和 TON + RIC）。我们在 TON 诱导后 5 天收集视网膜组织用于蛋白质印迹和组织化学分析。我们通过裂解的 caspase-3 免疫组织化学观察到与对照相比，TON 诱导的视网膜细胞死亡增加。此外，TON 队列显示 TUNEL 阳性细胞增加，RIC 显着减弱了这些细胞。免疫荧光数据显示，氧化应激标志物二氢乙锭 (DHE)、NOX-2 和硝基酪氨酸的表达在 TON 组中相对于对照组升高，而 RIC 治疗显着降低了这些标志物的表达水平。接下来，我们发现TON动物血浆中促炎细胞因子TNF-α增加，抗炎IL-10减少，RIC治疗逆转了这种表达水平。有趣的是，视网膜组织的蛋白质印迹显示，与对照组相比，TON 组的 RGC 标志物 Brn3a 和紧密连接蛋白（ZO-1 和 Occludin）以及 AMPKα1 表达下调。然而，RIC 显着增加了这些蛋白质的表达水平。这些数据共同表明，RIC 疗法激活了内源性保护机制，可减轻 TON 诱导的氧化应激和炎症，并改善 BRB 完整性。