Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark; Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark.
Exp Eye Res. 2018 Jun;171:174-182. doi: 10.1016/j.exer.2018.02.029. Epub 2018 Mar 2.
A dexamethasone (DEX) intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a DEX implant this study combined an experimental model of BRVO with proteomic techniques. In eight Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected into the right eye of each animal while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. DEX intervention reduced the retinal levels of platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor receptor 2 (VEGFR-2). DEX treatment resulted in increased levels of caveolin-1, peptidyl-prolyl cis-trans isomerase FKBP5 and transgelin. Changes in PDGFR-α and caveolin-1 were confirmed with immunohistochemistry. In BRVO treated with the DEX implant a strong reaction for caveolin-1 was observed in the innermost retinal layers. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier.
地塞米松（DEX）玻璃体内植入物（OZURDEX）为视网膜分支静脉阻塞（BRVO）继发炎症提供了有效的治疗方法。介导植入物有益效果的视网膜蛋白质组变化仍知之甚少。为了研究 BRVO 中 DEX 植入物干预后的视网膜蛋白质组变化，本研究将 BRVO 的实验模型与蛋白质组技术相结合。在 8 只丹麦兰德瑞斯猪中，使用氩激光在双眼中诱发实验性 BRVO。在诱发 BRVO 后，将 DEX 植入物注射到每只动物的右眼，而左眼对照眼给予相同的无植入物注射。BRVO 和 DEX 植入物干预 15 天后，切除视网膜并进行基于串联质量标签的质谱分析。共鉴定出 26 个明显改变的蛋白质。DEX 干预降低了血小板衍生生长因子受体-α（PDGFR-α）和血管内皮生长因子受体 2（VEGFR-2）的视网膜水平。DEX 治疗导致窖蛋白-1、肽基脯氨酰顺反异构酶 FKBP5 和转胶蛋白的水平增加。PDGFR-α 和窖蛋白-1 的变化通过免疫组织化学得到证实。在接受 DEX 植入物治疗的 BRVO 中，最内层视网膜层观察到窖蛋白-1的强烈反应。DEX 植入物干预可能通过降低 PDGFR-α 的视网膜水平来抑制 PDGF 信号，而窖蛋白-1 的含量增加可能有助于维持血视网膜屏障的完整性。
