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

被引：0

作者：

Tsai, Ming-Ling ^{[2
,5
,7
,8
]}

Horng, Chi-Ting ^{[4
,5
]}

Chen, Show-Li ^{[9
]}

Xiao, Xiao ^{[3
]}

Wang, Chih-Hung ^{[6
]}

Tsao, Yeou-Ping ^{[1
]}

机构：

[1] Mackay Mem Hosp, Dept Ophthalmol, Taipei, Taiwan

[2] Triserv Gen Hosp, Dept Ophthalmol, Taipei, Taiwan

[3] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA

[4] Kaohsiung Armed Force Gen Hosp, Dept Ophthalmol, Kaohsiung, Taiwan

[5] Tajen Univ, Dept Pharm, Pingtung, Taiwan

[6] Triserv Gen Hosp, Dept Otolaryngol Head & Neck Surg, Taipei, Taiwan

[7] Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan

[8] Natl Def Med Ctr, Dept Ophthalmol, Taipei, Taiwan

[9] Natl Taiwan Univ, Dept Microbiol & Immunol, Taipei 10764, Taiwan

来源：

MOLECULAR VISION | 2009年 / 15卷 / 164-65期

关键词：

ENDOTOXIN-INDUCED UVEITIS; GENE-TRANSFER; TRANSGENE EXPRESSION; VIRAL VECTORS; EYE DISEASE; THERAPY; INFLAMMATION; PREVENTION; ARTHRITIS; RESPONSES;

D O I：

暂无

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1 alpha 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 rAAVIL-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.

引用

页码：1542 / 1552

页数：11

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