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康柏西普高浓度、高频率玻璃体内注射兔眼安全性研究。

A safety study of high concentration and high frequency intravitreal injection of conbercept in rabbits.

机构信息

Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

Shenzhen Eye Hospital, Affiliated Shenzhen Eye Hospital of Jinan University, Shenzhen Key Laboratory of Ophthalmology, Shenzhen, China.

出版信息

Sci Rep. 2017 Apr 4;7(1):592. doi: 10.1038/s41598-017-00683-x.

Abstract

The novel anti-VEGF drug conbercept has been used in the treatment of several retinal neovascular diseases. Owning to the alteration of the structure, the newest drug is capable of combining more molecular targets and present higher affinity to the angiogenesis promoting factors. However, it is unknown whether it will cause any unwanted effects like other anti-VEGF agents. We studied the short-term safety of high concentration and high frequency intravitreal injection of conbercept in rabbits. Intraocular pressure, fundus-photography, ERGs were applied. Retinal morphology, the amount of apoptotic cells and protein levels of IL-6, IL-8 and TNF-α in the aqueous humor were determined. Retinal proteomics was detected using tandem mass tags (TMTs) quantitative mass spectrometry. The difference of IOP, ERGs, protein levels of inflammatory factors among rabbits received conbercept and PBS was not significant (P > 0.05). Fundus photographs and retinal morphology of animals in the conbercept-injected groups mimic those observed in the PBS-injected groups. No TUNEL-positive cell was seen in the retinal ganglion cell layer in the conbercept-injected groups. Proteomics did not show significant changes of inflammation or apoptosis associated proteins in the conbercept-injected eyes. We conclude that intravitreal injection of high concentration and high frequency conbercept is well tolerated at least in a short-term in rabbits.

摘要

新型抗血管内皮生长因子药物康柏西普已被用于多种视网膜新生血管疾病的治疗。由于结构的改变,这种新型药物能够结合更多的分子靶点,并对促进血管生成的因子表现出更高的亲和力。然而,它是否会像其他抗 VEGF 药物一样引起任何不良反应还不得而知。我们研究了高浓度和高频率玻璃体内注射康柏西普在兔眼的短期安全性。我们进行了眼压、眼底照相和 ERG 检查。检测房水中的细胞凋亡数量、IL-6、IL-8 和 TNF-α 蛋白水平以及视网膜形态。采用串联质量标签(TMTs)定量质谱法检测视网膜蛋白质组学。接受康柏西普和 PBS 注射的兔子的 IOP、ERGs 和炎症因子蛋白水平之间没有显著差异(P>0.05)。康柏西普注射组的眼底照片和视网膜形态与 PBS 注射组相似。在康柏西普注射组的视网膜神经节细胞层中未观察到 TUNEL 阳性细胞。蛋白质组学未显示康柏西普注射眼与炎症或细胞凋亡相关的蛋白有明显变化。我们的结论是,高浓度和高频率玻璃体内注射康柏西普在兔眼至少短期内是可以耐受的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9260/5428866/ccca6c8e0c6c/41598_2017_683_Fig1_HTML.jpg

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