Department of Ophthalmology, Odense University Hospital, Odense, Denmark.
Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark.
Mol Vis. 2024 Jul 2;30:268-277. eCollection 2024.
Ranibizumab is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Studying proteins that mediate the beneficial effects of ranibizumab in CRVO can potentially lead to the improved management of macular edema.
In 14 Danish Landrace pigs, experimental CRVO was induced in the right eyes and treated with either intravitreal ranibizumab (n = 6) or an intravitreal sodium chloride 9 mg/mL solution as a sham injection (n = 8). Successful CRVO was confirmed by fluorescein angiography. Retinal samples were collected 15 days after induced CRVO and analyzed with label-free, quantification, nano-liquid chromatography-tandem mass spectrometry. Validation was performed with western blotting and immunohistochemistry.
CRVO was successfully induced and confirmed by fluorescein angiography. A total of 28 proteins were upregulated, and 31 proteins were downregulated following ranibizumab treatment. A high concentration of the ranibizumab component immunoglobulin kappa chain C region was observed in retinas treated with ranibizumab. Complement C3, the Ig lambda chain C region, and nucleobindin-2 were downregulated following ranibizumab intervention. The downregulation of complement C3 was confirmed by western blotting. Modest changes were observed in the remaining significantly regulated proteins.
Retinal complement C3 was downregulated following ranibizumab intervention in CRVO. The decrease in complement C3 may potentially downregulate the inflammatory response in CRVO. A high retinal concentration of ranibizumab was reached 15 days after injection of the compound.
雷珠单抗是一种常用于治疗视网膜中央静脉阻塞（CRVO）后黄斑水肿的血管内皮生长因子（VEGF）抑制剂。研究介导雷珠单抗在 CRVO 中有益作用的蛋白质可能会改善黄斑水肿的管理。
在 14 只丹麦长白猪中，右眼诱导实验性 CRVO，并分别给予玻璃体内雷珠单抗（n = 6）或玻璃体内 9 mg/mL 氯化钠溶液作为假注射（n = 8）。通过荧光素血管造影术确认成功的 CRVO。在诱导 CRVO 后 15 天收集视网膜样本，并进行无标记、定量、纳米液相色谱-串联质谱分析。通过 Western blot 和免疫组织化学进行验证。
CRVO 通过荧光素血管造影术成功诱导并确认。雷珠单抗治疗后，有 28 种蛋白质上调，31 种蛋白质下调。在接受雷珠单抗治疗的视网膜中观察到高浓度的雷珠单抗成分免疫球蛋白 k 链 C 区。补体 C3、Ig lambda 链 C 区和核结合蛋白-2 在雷珠单抗干预后下调。补体 C3 的下调通过 Western blot 得到证实。其余显著调节蛋白观察到适度变化。
CRVO 中雷珠单抗干预后视网膜补体 C3 下调。补体 C3 的减少可能会下调 CRVO 中的炎症反应。在注射化合物 15 天后，视网膜中达到了高浓度的雷珠单抗。
