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编码白细胞介素-1受体拮抗剂的重组腺相关病毒载体对实验性葡萄膜炎的抑制作用。

Suppression of experimental uveitis by a recombinant adeno-associated virus vector encoding interleukin-1 receptor antagonist.

作者信息

Tsai Ming-Ling, Horng Chi-Ting, Chen Show-Li, Xiao Xiao, Wang Chih-Hung, Tsao Yeou-Ping

机构信息

Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan.

出版信息

Mol Vis. 2009 Aug 8;15:1542-52.

PMID:19693263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2723168/
Abstract

PURPOSE

To evaluate the potential of gene therapy with a recombinant adeno-associated virus vector encoding the interleukin-1 receptor antagonist gene (rAAV-IL-1Ra) in the treatment of experimental uveitis.

METHODS

The vitreal cavity of New Zealand white rabbits was injected with rAAV-IL-1Ra (4x10(7) infectious units), and the contralateral eye was injected with the same amount of rAAV-LacZ or PBS as a control. Transgene expression was evaluated by immunohistochemistry, ELISA, and RT-PCR. To evaluate the therapeutic potential of rAAV-IL-1Ra, experimental uveitis was induced by intravitreal injection of IL-1alpha at 10 and 100 days after rAAV-IL-1Ra administration. The effects of rAAV-IL-1Ra on experimental uveitis were investigated using histological and aqueous analysis.

RESULTS

Following intravitreal injection of rAAV-IL-1Ra, transgene expression was found in various cell types of the ocular tissues, such as ciliary epithelial cells, retinal ganglion cells, and retinal pigment epithelial cells. RT-PCR and ELISA showed that the IL-1Ra transgene persisted in the rabbit eye for at least 100 days. Compared with the control eyes, the transgene expression ameliorated experimental uveitis at 10 and 100 days after a single administration of rAAV-IL-1Ra.

CONCLUSIONS

Intravitreal administration of rAAV-IL-1Ra led to sustained human IL-1Ra transgene expression in rabbit eyes for 100 days. The transgene expression suppressed uveitis episodes at 10 and 100 days after rAAV-IL-1Ra injection. Long-term suppression of experimental uveitis could be achieved by gene therapy with rAAV-IL-1Ra.

摘要

目的

评估携带白细胞介素-1受体拮抗剂基因的重组腺相关病毒载体（rAAV-IL-1Ra）基因治疗实验性葡萄膜炎的潜力。

方法

向新西兰白兔的玻璃体腔注射rAAV-IL-1Ra（4×10⁷感染单位），对侧眼注射等量的rAAV-LacZ或PBS作为对照。通过免疫组织化学、酶联免疫吸附测定（ELISA）和逆转录-聚合酶链反应（RT-PCR）评估转基因表达。为评估rAAV-IL-1Ra的治疗潜力，在给予rAAV-IL-1Ra后10天和100天，通过玻璃体腔内注射白细胞介素-1α（IL-1α）诱导实验性葡萄膜炎。使用组织学和房水分析研究rAAV-IL-1Ra对实验性葡萄膜炎的影响。

结果

玻璃体腔内注射rAAV-IL-1Ra后，在眼组织的各种细胞类型中发现了转基因表达，如睫状体上皮细胞、视网膜神经节细胞和视网膜色素上皮细胞。RT-PCR和ELISA显示，IL-1Ra转基因在兔眼中持续存在至少100天。与对照眼相比，单次给予rAAV-IL-1Ra后10天和100天，转基因表达改善了实验性葡萄膜炎。

结论

玻璃体腔内注射rAAV-IL-1Ra导致人IL-1Ra转基因在兔眼中持续表达100天。rAAV-IL-1Ra注射后10天和100天，转基因表达抑制了葡萄膜炎发作。rAAV-IL-1Ra基因治疗可实现对实验性葡萄膜炎的长期抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/0a17595d41b4/mv-v15-1542-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/87ae2568cd00/mv-v15-1542-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/9c09cfd95e2e/mv-v15-1542-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/a1905473ebf4/mv-v15-1542-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/b04c02f6fbe8/mv-v15-1542-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/dda97f34b82d/mv-v15-1542-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/2e8601b8df82/mv-v15-1542-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/0a17595d41b4/mv-v15-1542-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/87ae2568cd00/mv-v15-1542-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/9c09cfd95e2e/mv-v15-1542-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/a1905473ebf4/mv-v15-1542-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/b04c02f6fbe8/mv-v15-1542-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/dda97f34b82d/mv-v15-1542-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/2e8601b8df82/mv-v15-1542-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/2723168/0a17595d41b4/mv-v15-1542-f7.jpg

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