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

Abstract

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 itsmore » ability to inhibit the pro-angiogenic effects of PDGF-BB.« less

Authors:
; ;  [1]; ; ;  [2]; ;  [1];  [1]
  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)
Publication Date:
OSTI Identifier:
22416865
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 456; Journal 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)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; DOSES; GROWTH FACTORS; IN VITRO; LIPOPROTEINS; MALES; MESSENGER-RNA; MICE; RECEPTORS; RETINA

Citation Formats

Kim, Junghyun, Kim, Chan-Sik, Jo, Kyuhyung, Cho, Yun-Seok, Kim, Hyun-Gyu, Lee, Geun-Hyeog, Lee, Yun Mi, Sohn, Eunjin, and Kim, Jin Sook, E-mail: jskim@kiom.re.kr. HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2014.11.033.
Kim, Junghyun, Kim, Chan-Sik, Jo, Kyuhyung, Cho, Yun-Seok, Kim, Hyun-Gyu, Lee, Geun-Hyeog, Lee, Yun Mi, Sohn, Eunjin, & Kim, Jin Sook, E-mail: jskim@kiom.re.kr. HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice. United States. doi:10.1016/J.BBRC.2014.11.033.
Kim, Junghyun, Kim, Chan-Sik, Jo, Kyuhyung, Cho, Yun-Seok, Kim, Hyun-Gyu, Lee, Geun-Hyeog, Lee, Yun Mi, Sohn, Eunjin, and Kim, Jin Sook, E-mail: jskim@kiom.re.kr. Fri . "HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice". United States. doi:10.1016/J.BBRC.2014.11.033.
@article{osti_22416865,
title = {HL-217, a new topical anti-angiogenic agent, inhibits retinal vascular leakage and pathogenic subretinal neovascularization in Vldlr{sup −/−} mice},
author = {Kim, Junghyun and Kim, Chan-Sik and Jo, Kyuhyung and Cho, Yun-Seok and Kim, Hyun-Gyu and Lee, Geun-Hyeog and Lee, Yun Mi and Sohn, Eunjin and Kim, Jin Sook, E-mail: jskim@kiom.re.kr},
abstractNote = {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.},
doi = {10.1016/J.BBRC.2014.11.033},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 456,
place = {United States},
year = {Fri Jan 02 00:00:00 EST 2015},
month = {Fri Jan 02 00:00:00 EST 2015}
}