Interferon-γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy.

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.

• Authors: Inseong Jung, Dokyung Jung, Zhao Zha, Jongwon Jeong, Soojeong Noh, Jiwon Shin, Jun-Kook Park, Kwang-Soo Kim, Youngtae Jeong, Jin Hur, Moon-Chang Baek, Sophia Diaz-Aguilar, Edith Aguilar, Martin Friedlander, Felicitas Bucher, Kyungmoo Yea
• Journal: Cytokine (Cytokine) Vol. 143 Pg. 155542 (07 2021) ISSN: 1096-0023 [Electronic] England
• PMID: 33926775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• STAT1 Transcription Factor
• Interferon-gamma

Topics

• Animals
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Hypoxia (complications)
• Interferon-gamma (administration & dosage, pharmacology, therapeutic use)
• Intravitreal Injections
• Ischemia (complications)
• Mice
• Neovascularization, Physiologic (drug effects)
• Retina (drug effects, pathology, physiopathology)
• Retinal Neovascularization (complications, drug therapy, physiopathology)
• STAT1 Transcription Factor (metabolism)
• Signal Transduction (drug effects)