UTMD"可逆开闭"血视网膜屏障联合rAAV-MERTK治疗视网膜色素变性的实验研究

项目名称： UTMD"可逆开闭"血视网膜屏障联合rAAV-MERTK治疗视网膜色素变性的实验研究

项目编号： No.81200700

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 李红丽

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 血视网膜屏障(blood-retina barrier, BRB)被认为是阻碍基因进入视网膜的主要原因。克服BRB输送基因是一项具有挑战性的工作，至今尚无有效的方法。超声靶向破坏微泡（ultrasound targeted microbubble destruction，UTMD）为克服BRB提供了可能。UTMD可在细胞间或细胞膜上产生一过性的空隙，促使基因进入组织和细胞。我们前期实验证实UTMD能够有效提高rAAV2-EGFP转染视网膜的效率。本研究设想在适合的条件下UTMD能够靶向"可逆开闭"BRB，探寻"可逆开闭"的机制及其对视功能的影响，探索视网膜基因输送的新方法。借此方法用rAAV-MERTK转染皇家科学院大鼠，考察UTMD联合rAAV-MERTK 对视网膜色素变性的治疗效果。如果能够有效解决BRB阻碍基因输送的难题，将为视网膜疾病基因治疗提供方便、安全、有效的输送系统。

中文关键词： 血视网膜屏障；微泡；超声；视网膜色素变性；MERTK

英文摘要： Blood-retina barrier(BRB),is regarded as the main reason that impedes genes entering the retina. To conquer BRB is a challenging task, there is no safe and effective way found up to now. Ultrasound targeted microbubble destruction (UTMD), provides possibility for conquering BRB. UTMD can make a transient core on the cell membrane or among the cells, thus urge the genes to enter tissue and cells. Our previous experiment proved that UTMD could be used safely to enhance rAAV2-EGFP(type 2 recombinant adeno-associated viral vectors encoding enhanced green fluorescent protein)transfection efficiency of rat retina. This project assumes that UTMD can target the reversible opening and closing BRB under compatible conditions, search for the mechanism of the reversible opening and closing BRB as well as its effects on the visual function, and explore the new method of the transportation of the retina genes. Based on this way, we use rAAV-MERTK to infect Royal College of Surgeons (RCS), so as to evaluate the therapeutic effects of the UTMD combined rAAV-MERTK on retinitis pigmentosa. If it can solve the tough problem of the gene delivery blocked by BRB, it will provide the gene therapy of retinal diseases with a convenient, safe and effective transfection system.

英文关键词： Blood-retina barrier；Microbubble；Ultrasound；Retinitis pigmentosa；MERTK