Complement C3 is downregulated following ranibizumab intervention in experimental central retinal vein occlusion.

IF 1.8 3区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2024-07-02 eCollection Date: 2024-01-01
Lasse Jørgensen Cehofski, Anders Kruse, Mads Odgaard Mæng, Benedict Kjaergaard, Benn Falch Sejergaard, Anders Schlosser, Grith Lykke Sorensen, Bent Honoré, Henrik Vorum
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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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雷尼珠单抗干预实验性视网膜中央静脉闭塞后,补体C3下调。
目的雷珠单抗是一种常用的血管内皮生长因子(VEGF)抑制剂,用于治疗视网膜中央静脉闭塞(CRVO)后的黄斑水肿。研究介导雷尼珠单抗对CRVO有益作用的蛋白质有可能改善黄斑水肿的治疗:方法:在14头丹麦陆地猪的右眼中诱导实验性CRVO,并用玻璃体内注射雷尼珠单抗(6头)或玻璃体内注射9毫克/毫升氯化钠溶液作为假注射(8头)。通过荧光素血管造影确认 CRVO 成功。在诱导 CRVO 15 天后收集视网膜样本,并采用无标记、定量、纳米液相色谱-串联质谱法进行分析。结果:结果:成功诱导了 CRVO,并通过荧光素血管造影证实了这一点。雷尼珠单抗治疗后,共有28种蛋白质上调,31种蛋白质下调。在使用雷尼珠单抗治疗的视网膜中观察到高浓度的雷尼珠单抗成分免疫球蛋白卡帕链C区。雷尼珠单抗干预后,补体C3、免疫球蛋白λ链C区和核卞蛋白-2下调。补体 C3 的下调已通过 Western 印迹技术得到证实。其余受显著调节的蛋白质变化不大:结论:雷尼珠单抗干预 CRVO 后,视网膜补体 C3 下调。补体C3的减少可能会降低CRVO的炎症反应。注射雷尼珠单抗15天后,视网膜中的雷尼珠单抗浓度达到较高水平。
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来源期刊
Molecular Vision
Molecular Vision 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
25
审稿时长
1 months
期刊介绍: Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.
期刊最新文献
Erratum: A method for gene knockdown in the retina using a lipid-based carrier. Increased inflammatory mediators in the ocular surface tissue in keratoconus. Retraction: Swati Arora, Nagendra Verma. Exosomal microRNAs as potential biomarkers and therapeutic targets in corneal diseases. Molecular Vision 2024; 30:92-106. Complement C3 is downregulated following ranibizumab intervention in experimental central retinal vein occlusion. A potential novel role of the R36P mutation in CRYGD in congenial cataract.
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