Cehofski Lasse Jørgensen, Kruse Anders, Bøgsted Martin, Magnusdottir Sigriður Olga, Stensballe Allan, Honoré Bent, Vorum Henrik
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. 2016 Nov;152:49-56. doi: 10.1016/j.exer.2016.09.002. Epub 2016 Sep 9.
Animal models of experimental branch retinal vein occlusion (BRVO) provide a unique opportunity to study protein changes directly in retinal tissue. Results from these experimental models suggest that experimental BRVO is associated with an upregulation of extracellular matrix remodeling and adhesion signaling processes. To study whether these processes could be blocked by inhibition of VEGF-A, a porcine model of experimental BRVO was combined with proteomic analyses. In six Danish Landrace pigs experimental BRVO was induced with argon laser in both eyes. After 24 h an injection of 0.05 mL ranibizumab was given in the right eyes of the animals while left eyes received an injection of 0.05 mL 9 mg/mL sodium chloride water. Retinas were dissected three days after BRVO and the retinal samples were analyzed with label-free quantification as well as tandem mass tag based proteomics. In retinas treated with ranibizumab five proteins exhibited statistically significant changes in content with both proteomic techniques. These five proteins, which were all decreased in content, included integrin β-1, peroxisomal 3-ketoacyl-CoA thiolase, OCIA domain-containing protein 1, calnexin and 40S ribosomal protein S5. As anti-integrin therapies are under development for inhibition of angiogenesis in retinal diseases it is interesting that inhibition of VEGF-A in itself resulted in a small decrease in the content of integrin β-1. The decreased content of integrin β-1 indicates that extracellular matrix remodeling and adhesion processes associated with BRVO are at least partly reversed through inhibition of VEGF-A.
实验性视网膜分支静脉阻塞（BRVO）的动物模型为直接研究视网膜组织中的蛋白质变化提供了独特的机会。这些实验模型的结果表明，实验性BRVO与细胞外基质重塑和黏附信号传导过程的上调有关。为了研究这些过程是否可以通过抑制血管内皮生长因子A（VEGF-A）来阻断，将实验性BRVO的猪模型与蛋白质组学分析相结合。在六只丹麦长白猪中，双眼用氩激光诱导实验性BRVO。24小时后，给动物的右眼注射0.05 mL雷珠单抗，而左眼注射0.05 mL 9 mg/mL氯化钠溶液。BRVO三天后解剖视网膜，并用无标记定量以及基于串联质量标签的蛋白质组学分析视网膜样本。在接受雷珠单抗治疗的视网膜中，两种蛋白质组学技术均显示有五种蛋白质的含量发生了统计学上的显著变化。这五种蛋白质的含量均降低，包括整合素β-1、过氧化物酶体3-酮酰基辅酶A硫解酶、含OCIA结构域蛋白1、钙连蛋白和40S核糖体蛋白S5。由于正在开发抗整合素疗法以抑制视网膜疾病中的血管生成，因此有趣的是，抑制VEGF-A本身会导致整合素β-1的含量略有下降。整合素β-1含量的降低表明，与BRVO相关的细胞外基质重塑和黏附过程至少部分地通过抑制VEGF-A而得到逆转。
