Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin

被引：37

作者：

Nakama, T. ^{[1
]}

Yoshida, S. ^{[1
]}

Ishikawa, K. ^{[1
]}

Kobayashi, Y. ^{[1
]}

Zhou, Y. ^{[1
]}

Nakao, S. ^{[1
]}

Sassa, Y. ^{[1
,2
]}

Oshima, Y. ^{[1
]}

Takao, K. ^{[3
]}

Shimahara, A. ^{[3
]}

Yoshikawa, K. ^{[3
]}

Hamasaki, T. ^{[4
]}

Ohgi, T. ^{[4
]}

Hayashi, H. ^{[4
]}

Matsuda, A. ^{[5
]}

Kudo, A. ^{[6
]}

Nozaki, M. ^{[7
]}

Ogura, Y. ^{[7
]}

Kuroda, M. ^{[8
]}

Ishibashi, T. ^{[1
]}

机构：

[1] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Fukuoka 8128582, Japan

[2] Fukuoka Univ, Chikushi Hosp, Dept Ophthalmol, Fukuoka 81401, Japan

[3] AQUA Therapeut Co Ltd, Kobe, Hyogo, Japan

[4] BIO Factory, BONAC Corp, Strateg Headquarters Res & Dev, Fukuoka, Japan

[5] Juntendo Univ, Sch Med, Dept Ophthalmol, Tokyo 113, Japan

[6] Tokyo Inst Technol, Dept Biol Informat, Yokohama, Kanagawa 227, Japan

[7] Nagoya City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med Sci, Nagoya, Aichi, Japan

[8] Tokyo Med Univ, Dept Mol Pathol, Tokyo 1608402, Japan

来源：

GENE THERAPY | 2015年 / 22卷 / 02期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

PROLIFERATIVE DIABETIC-RETINOPATHY; SUBRETINAL NEOVASCULAR MEMBRANES; DEGENERATION TREATMENTS TRIALS; OXYGEN-INDUCED RETINOPATHY; PIGMENT EPITHELIAL-CELLS; TOLL-LIKE RECEPTOR-3; MACULAR DEGENERATION; GROWTH-FACTOR; GEOGRAPHIC ATROPHY; MOUSE MODEL;

D O I：

10.1038/gt.2014.112

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：

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.

引用

页码：127 / 137

页数：11

共 51 条

[1] Involvement of Periostin in Regression of Hyaloidvascular System during Ocular Development [J].