Interferon‐γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy. (July 2021)

• Record Type: Journal Article
• Authors: Jung, Inseong; Jung, Dokyung; Zha, Zhao; Jeong, Jongwon; Noh, Soojeong; Shin, Jiwon; Park, Jun-Kook; Kim, Kwang-Soo; Jeong, Youngtae; Hur, Jin; Baek, Moon-Chang; Diaz-Aguilar, Sophia; Aguilar, Edith; Friedlander, Martin; Bucher, Felicitas; Yea, Kyungmoo
• Is Part Of: Cytokine. Volume 143(2021)
• Publication Date: 2021-07
• Subjects: IFNG -- Angiogenesis -- VEGFa -- Wound healing -- Tube formation -- Endothelial cells; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2021.155542
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IFNG suppresses VEGFa-induced angiogenesis in endothelial cells. The anti-angiogenic effect of IFNG is dependent on STAT1 signaling. IFNG prevents hypoxia-induced retinal neovascularization in vivo. Abstract: Interferon‐γ (IFNG) is one of the key cytokines that regulates both innate and adaptive immune responses in the body. However, the role of IFNG in the regulation of vascularization, especially in the context of Vascular endothelial growth factor A (VEGFa)-induced angiogenesis is not clarified. Here, we report that IFNG shows potent anti-angiogenic potential against VEGFa-induced angiogenesis. IFNG significantly inhibited proliferation, migration, and tube formation of Human umbilical vein endothelial cells (HUVECs) both under basal and VEGFa-treated conditions. Intriguingly, Knockdown (KD) of STAT1 abolished the inhibitory effect of IFNG on VEGFa-induced angiogenic processes in HUVECs. Furthermore, IFNG exhibited potent anti-angiogenic efficacy in the mouse model of oxygen-induced retinopathy (OIR), an in vivo model for hypoxia-induced retinal neovascularization, without induction of functional side effects. Taken together, these results show that IFNG plays a crucial role in the regulation of VEGFa-dependent angiogenesis, suggesting its potential therapeutic applicability in neovascular diseases.