机构：[1]Xiamen Eye Center, Xiamen University, Xiamen, China[2]Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, School of Optometry, Shenzhen University, Shenzhen, China[3]Institute of Laboratory Animal Sciences, Sichuan Academy of Medical Sciences, Provincial People’s Hospital, Chengdu, Sichuan, China四川省人民医院[4]Chengdu Institute of Biology, Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China四川省人民医院[5]Ocular Gene Therapy Core, National Eye Institute, NIH, 6 Center Drive, Room 307, Bethesda, MD 20892, USA[6]Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Primary open-angle glaucoma (POAG) is considered a lifelong disease characterized by optic nerve deterioration and visual field damage. Although the disease progression can usually be controlled by lowering the intraocular pressure (IOP), therapeutic effects of current approaches do not last long. Gene therapy could be a promising method for persistent treatment of the disease. Our previous study demonstrated that gene transfer of exoenzyme C3 transferase (C3) to the trabecular meshwork (TM) to inhibit Rho GTPase (Rho), the upstream signal molecule of Rho-associated kinase (ROCK), resulted in lowered IOP in normal rodent eyes. In the present study, we show that the lentiviral vector (LV)-mediated C3 expression inactivates RhoA in human TM cells by ADP ribosylation, resulting in disruption of the actin cytoskeleton and altered cell morphology. In addition, intracameral delivery of the C3 vector to monkey eyes leads to persistently lowered IOP without obvious signs of inflammation. This is the first report of using a vector to transduce the TM of an alive non-human primate with a gene that alters cellular machinery and physiology. Our results in non-human primates support that LV-mediated C3 expression in the TM may have therapeutic potential for glaucoma, the leading cause of irreversible blindness in humans.
基金：
This study was supported by grants from the National Natural Science
Foundation of China (NSFC) (81770924 and 81500718), the
Sanming Project of Medicine in Shenzhen (SZSM201512045),
the National Key Scientific Research Program (2015CB554100), and
the Department of Science and Technology of Sichuan Province
(2016TD0009).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|1 区医学
小类|1 区生物工程与应用微生物1 区医学：研究与实验2 区遗传学
最新[2023]版：
大类|1 区医学
小类|1 区生物工程与应用微生物1 区遗传学1 区医学：研究与实验
JCR分区：
出版当年[2017]版：
Q1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGY
最新[2023]版：
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTAL
第一作者机构：[1]Xiamen Eye Center, Xiamen University, Xiamen, China[2]Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, School of Optometry, Shenzhen University, Shenzhen, China
共同第一作者：
通讯作者：
通讯机构：[1]Xiamen Eye Center, Xiamen University, Xiamen, China[2]Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, School of Optometry, Shenzhen University, Shenzhen, China[*1]Xiamen Eye Center, Xiamen University, 336 Xiahe Road, 361001 Xiamen, China.
推荐引用方式(GB/T 7714)：
Junkai Tan,Guo Liu,Xianjun Zhu,et al.Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys[J].MOLECULAR THERAPY.2019,27(7):1327-1338.doi:10.1016/j.ymthe.2019.04.021.
APA：
Junkai Tan,Guo Liu,Xianjun Zhu,Zhijian Wu,Ningli Wang...&Xuyang Liu.(2019).Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys.MOLECULAR THERAPY,27,(7)
MLA：
Junkai Tan,et al."Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys".MOLECULAR THERAPY 27..7(2019):1327-1338
医学