HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr-/- mice

被引：7

作者：

Kim, Junghyun ^{[1
]}

Kim, Chan-Sik ^{[1
]}

Jo, Kyuhyung ^{[1
]}

Cho, Yun-Seok ^{[2
]}

Kim, Hyun-Gyu ^{[2
]}

Lee, Geun-Hyeog ^{[2
]}

Lee, Yun Mi ^{[1
]}

Sohn, Eunjin ^{[1
]}

Kim, Jin Sook ^{[1
]}

机构：

[1] Korea Inst Oriental Med, Herbal Med Res Div, Korean Med Based Herbal Drug Dev Grp, Taejon 305811, South Korea

[2] Hanlim Pharm Co Ltd, Ctr Res & Dev, Seoul, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 456卷 / 01期

关键词：

Subretinal neovascularization; HL-217; Platelet derived growth factor; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; MACULAR DEGENERATION; OCULAR NEOVASCULARIZATION; ANGIOMATOUS PROLIFERATION; INTRAVITREAL INJECTION; IN-VITRO; PDGF-B; EXPRESSION; VEGF;

D O I：

10.1016/j.bbrc.2014.11.033

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：

HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (VIdlr(-/-)) mice. In three-week-old male Vldlr(-/-) mice, HL-217 (1.5 or 3 mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFR beta interaction was evaluated in vitro. The neovascular area in the Vldlr(-/-) mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGFBB/PDGFR beta interaction (IC50 = 38.9 +/- 0.7 mu M). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：53 / 58

页数：6