Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα and PDGFR Targets

• Published in: Scientific reports Vol. 6; no. 1; p. 30843
• Main Authors: Zong, Yao, Yuan, Yongguang, Qian, Xiaobing, Huang, Zhen, Yang, Wei, Lin, Leilei, Zheng, Qishan, Li, Yujie, He, Huining, Gao, Qianying
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-08-2016; Nature Publishing Group
• Subjects: 13/51; 631/154; 692/308; Animals; Artemisinins - pharmacology; Humanities and Social Sciences; Macaca fascicularis; Macular Edema - metabolism; Macular Edema - pathology; Macular Edema - prevention & control; Male; multidisciplinary; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - prevention & control; Pilot Projects; Protein Kinase C-alpha - antagonists & inhibitors; Protein Kinase C-alpha - metabolism; Rabbits; Receptors, Platelet-Derived Growth Factor - antagonists & inhibitors; Receptors, Platelet-Derived Growth Factor - metabolism; Retinal Neovascularization - metabolism; Retinal Neovascularization - pathology; Retinal Neovascularization - prevention & control; Science; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30843

Ocular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20–30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 μg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets.