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重组单链尿激酶型纤溶酶原激活剂在兔视网膜静脉阻塞模型中的溶栓疗效及安全性

Thrombolytic efficacy and safety of recombinant scu-PA in a rabbit retinal vein occlusion model.

作者信息

Yu Dawei, Rong Hua, Xing Dongjun, Hu Liying, Wen Yinping, Wang Xiangyang, Zhang Weiran, Fan Hao, Zhao Yi, Gong Xue, Chen Lu, Ma Xiaohui, Li Zhiqing

机构信息

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, China.

Center for Integrated Innovation, Tasly Academy, Tasly Pharmaceutical Group Co., Ltd., Tianjin, 300410, China.

出版信息

Eur J Pharmacol. 2025 Mar 15;991:177293. doi: 10.1016/j.ejphar.2025.177293. Epub 2025 Jan 23.

Abstract

Retinal vein occlusion (RVO) has become the second most common retinal vascular disease after diabetic retinopathy. Existing therapeutic approaches, including intravitreal injection of antivascular endothelial growth factors (anti-VEGFs) and/or glucocorticoids and laser therapy, primarily address secondary macular edema and neovascularisation. However, these strategies do not address the underlying cause of the disease and may have harmful side effects. There is an urgent need for therapies that have a better prognosis and include the administration of thrombolytics at an early stage. Therefore, in the present study, we investigated the thrombolytic effect of treatment with recombinant human Single-chain urokinase-type plasminogen activators (scu-PA)and the differences in its efficacy at different doses in a rabbit RVO model. In addition, through a series of ophthalmological examinations, such as optical coherence tomography (OCT) and electrophysiology, conducted to ascertain the effects of treatment with scu-PA on the ocular fibrinolytic system, we noted a definitive safety window for the vitreous administration of scu-PA. Therefore, this study is the first to confirm that an intravenous or vitreous cavity injection of scu-PA has definitive potential for treating RVO; however, additional clinical studies are needed for further validation.

摘要

视网膜静脉阻塞(RVO)已成为仅次于糖尿病性视网膜病变的第二常见视网膜血管疾病。现有的治疗方法,包括玻璃体内注射抗血管内皮生长因子(抗VEGF)和/或糖皮质激素以及激光治疗,主要针对继发性黄斑水肿和新生血管形成。然而,这些策略并未解决该疾病的根本原因,并且可能具有有害的副作用。迫切需要具有更好预后且包括在早期给予溶栓剂的治疗方法。因此,在本研究中,我们在兔RVO模型中研究了重组人单链尿激酶型纤溶酶原激活剂(scu-PA)治疗的溶栓作用及其不同剂量疗效的差异。此外,通过进行一系列眼科检查,如光学相干断层扫描(OCT)和电生理学检查,以确定scu-PA治疗对眼部纤溶系统的影响,我们注意到scu-PA玻璃体内给药存在明确的安全窗。因此,本研究首次证实静脉内或玻璃体腔注射scu-PA具有治疗RVO的明确潜力;然而,需要进一步的临床研究进行进一步验证。

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