当前位置: X-MOL 学术Exp. Eye Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of aflibercept on proliferative vitreoretinopathy: Proteomic analysis in an experimental animal model
Experimental Eye Research ( IF 3.0 ) Pub Date : 2021-01-05 , DOI: 10.1016/j.exer.2020.108425
Isil Uslubas , Aylin Kanli , Murat Kasap , Gurler Akpinar , Levent Karabas

Purpose

The aim of this study was to monitor inflammatory, proliferative and progressive effects of proliferative vitreoretinopathy (PVR) and aflibercept treatment in dispase induced PVR rat model by proteomic analysis.

Material and methods

A total of 35 male Long Evans pigmented rats were divided into three groups, namely, PVR (dispase+saline), PVR+aflibercept (dispase+aflibercept) and control. The PVR group received 2 μl of 0.03 IU/μl dispase and 2 μl saline, the PVR+aflibercept group received 2 μl of 0.03 IU/μl and 2 μl of 40 mg/ml aflibercept at the first day of the experiment. At the end of the 6th week all retina and vitreous specimens were collected by evisceration and transferred to the proteomics laboratory for analysis. Proteomic analysis by 2D gel electrophoresis coupled with MALDI-TOF/TOF was performed.

Results

In the PVR and PVR+aflibercept group 16 different proteins that were identified to be differentially regulated in comparison to the control group. In the PVR+aflibercept group, ENO1, ENO2, LDH-B, PEBP-1 and GS levels were higher than the PVR group. In addition, the association of proteins such as UCHL, PEBP1, PDHB and ENO1 with PVR has been demonstrated for the first time.

Conclusion

STRING analysis elucidated the functional protein-protein interaction among the differentially regulated proteins and highlighted that those proteins mainly played roles in carbon and nucleotide metabolisms. Functional analysis of the differentially regulated proteins indicated the presence of inflammation, gliosis and retinal damage in the PVR group. Aflibercept treatment had pronounced effect on prevention of inflammation and retinal damage while causing a slight increase in gliosis. However, aflibercept treatment was not effective enough to normalize the levels of differentially regulated proteins of the PVR group. Therefore, we predict that the treatment dose of aflibercept used in this study was below of its ideal concentration and should be increased in the future studies. The differential regulation of these structural proteins in this study should shed some light to the mechanism of glial wound formation in the retina and guide future treatment modalities.



中文翻译:

阿柏西普对增生性玻璃体视网膜病变的影响:实验动物模型中的蛋白质组学分析

目的

这项研究的目的是通过蛋白质组分析监测增殖性玻璃体视网膜病变(PVR)和阿柏西普治疗在分散性PVR大鼠模型中的炎症,增殖和进行性作用。

材料与方法

总共35只雄性Long Evans有色大鼠被分成三组,即PVR(分散酶+盐水),PVR +阿非西普(分散酶+阿非西普)和对照组。在实验的第一天,PVR组接受2μl的0.03 IU /μl分散酶和2μl盐水,PVR + aflibercept组接受2μl的0.03 IU /μl和2μl40 mg / ml的阿柏西普。在第6周结束时,通过剔除收集所有视网膜和玻璃体标本,并将其转移到蛋白质组学实验室进行分析。通过结合MALDI-TOF / TOF的2D凝胶电泳进行蛋白质组学分析。

结果

在PVR和PVR + aflibercept组中,与对照组相比,有16种不同的蛋白质被确定具有不同的调控作用。在PVR + aflibercept组中,ENO1,ENO2,LDH-B,PEBP-1和GS的水平高于PVR组。此外,首次证明了诸如UCHL,PEBP1,PDHB和ENO1等蛋白质与PVR的关联。

结论

STRING分析阐明了差异调节蛋白之间的功能性蛋白-蛋白相互作用,并强调了这些蛋白主要在碳和核苷酸代谢中发挥作用。对差异调节蛋白的功能分析表明,PVR组存在炎症,神经胶质增生和视网膜损伤。阿柏西普治疗对预防炎症和视网膜损伤有明显作用,同时引起胶质增生略有增加。但是,阿柏西普治疗不足以正常化PVR组差异调节蛋白的水平。因此,我们预测本研究中使用的阿柏西普治疗剂量低于其理想浓度,在以后的研究中应增加治疗剂量。

更新日期:2021-01-10
down
wechat
bug