Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1α/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization

Jiaowen Xu; Yuanyuan Tu; Ying Wang; Xun Xu; Xiaodong Sun; Laiqing Xie; Qingliang Zhao; Yang Guo; Yonghui Gu; Jingxia Du; Shu Du; Manhui Zhu; E. Song

Biomedicine & Pharmacotherapy (Jan 2020)

Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1α/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization

Jiaowen Xu,
Yuanyuan Tu,
Ying Wang,
Xun Xu,
Xiaodong Sun,
Laiqing Xie,
Qingliang Zhao,
Yang Guo,
Yonghui Gu,
Jingxia Du,
Shu Du,
Manhui Zhu,
E. Song

Affiliations

Jiaowen Xu: Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Yuanyuan Tu: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China
Ying Wang: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China; Department of Ophthalmology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
Xun Xu: Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China; Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
Xiaodong Sun: Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China; Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
Laiqing Xie: Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Qingliang Zhao: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China
Yang Guo: Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Yonghui Gu: Department of Ophthalmology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China
Jingxia Du: Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Shu Du: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China
Manhui Zhu: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China; Corresponding authors at: Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China.
E. Song: Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China; Corresponding authors at: Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China.

Journal volume & issue: Vol. 121
p. 109606

Abstract

Read online

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly and is attributed to choroidal neovascularization (CNV), which is a feature of wet AMD. The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to the pathogenesis of CNV. M1-type macrophages/microglia secrete interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), facilitating the development of CNV. Epigallocatechin-3-gallate (EGCG) is a kind of polyphenol in green tea that exerts anti-inflammatory and antiangiogenic effects. In this study, a prodrug of EGCG (pro-EGCG) alleviated mouse laser-induced CNV leakage and reduced CNV area by down-regulating HIF-1α/VEGF/VEGFR2 pathway; M1-type macrophage/microglia polarization; as well as endothelial cell viability, proliferation, migration and tube formation, indicating a novel potential therapy for AMD.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

About the journal

Abstract

Keywords