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 VisionPub Date : 2024-07-02eCollection 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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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).
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