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

Journal Article · Fri Jan 02 00:00:00 EST 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.11.033· OSTI ID:22416865

Kim, Junghyun; Kim, Chan-Sik; Jo, Kyuhyung ^[1]; Cho, Yun-Seok; Kim, Hyun-Gyu; Lee, Geun-Hyeog ^[2]; Lee, Yun Mi; Sohn, Eunjin ^[1]

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1. Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of)
2. Research and Development Center, Hanlim Pharm. Co. Ltd., 1656-10, Seocho-dong, Seocho-gu, Seoul (Korea, Republic of)

Highlights: • HL-217 is a new synthetic topical anti-angiogenic agent. • HL-217 attenuated subretinal neovascularization in Vldlr{sup −/−} mice. • HL-217 blocked the binding of PDGF-BB to PDGFRβ. - Abstract: 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 (Vldlr{sup −/−}) mice. In three-week-old male Vldlr{sup −/−} 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/PDGFRβ interaction was evaluated in vitro. The neovascular area in the Vldlr{sup −/−} 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 PDGF-BB/PDGFRβ interaction (IC{sub 50} = 38.9 ± 0.7 μM). 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.

• OSTI ID: 22416865
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 456, Issue 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOGENESIS
DOSES
GROWTH FACTORS
IN VITRO
LIPOPROTEINS
MALES
MESSENGER-RNA
MICE
RECEPTORS
RETINA