Journal
VASCULAR PHARMACOLOGY
Volume 90, Issue -, Pages 19-26Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2016.07.007
Keywords
Betaine; Oxygen induced retinopathy; Reactive oxygen species; Retinal neovascularization; Vascular endothelial growth factor
Categories
Funding
- Seoul National University Hospital Research Fund [03-2014-0260]
- MD-PhD program of Korea Research Institute of Bioscience and Biotechnology
- Pioneer Research Program of the National Research Foundation of Korea/Ministry of Education, Science and Technology [2012-0009544]
- Bio & Medical Technology Development Program of the National Research Foundation - Korean government, MSIP [2015M3A9E6028949]
- Development of Platform Technology for Innovative Medical Measurements Program from the Korea Research Institute of Standards and Science [KRISS-2016-16011064]
- Food Functionality Evaluation program under the Ministry of Agriculture, Food and Rural Affairs
- Korea Food Research Institute
- National Research Foundation of Korea [2015M3A9E6028949] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Reactive oxygen species (ROS) as well as vascular endothelial growth factor (VEGF) play important roles in pathologic retinal neovascularization. We investigated whether betaine inhibits pathologic retinal neovascularization in a mouse model of oxygen induced retinopathy (OIR). Betaine was intravitreally injected in OIR mice at postnatal day (P) 14. At P17, the neovascular tufts area in OIR retina was analyzed. Intravitreal injection of betaine (200 mu M) effectively reduced the neovascular tufts area in OIR retina (68.0 +/- 6.7% of the control eyes, P < 0.05). Even in a high concentration (2 mM), betaine never induced any retinal toxicity or cytotoxicity. Betaine significantly inhibited VEGF-induced proliferation, migration, and tube formation in human retinal microvascular endothelial cells (HRMECs). Betaine suppressed VEGF-induced VEGFR-2, Akt and ERIC phosphorylation in HRMECs. In human brain astrocytes, betaine reduced tBH-induced ROS production, and subsequently attenuated tBH-induced VEGFA mRNA transcription via suppression of ROS. Our data suggest that betaine has an anti-angiogenic effect on pathologic retinal neovascularization via suppression of ROS mediated VEGF signaling. Betaine could be a potent anti-angiogenic agent to treat pathologic retinal neovascularization. (C) 2016 Elsevier Inc. All rights reserved.
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