Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy

Yedi Zhou, Shigeo Yoshida, Yuki Kubo, Yoshiyuki Kobayashi, Takahito Nakama, Muneo Yamaguchi, Keijiro Ishikawa, Shintaro Nakao, Yasuhiro Ikeda, Tatsuro Ishibashi, Koh Hei Sonoda

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Abstract

Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization.

Original languageEnglish
Article number28140
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jun 17 2016

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Pathologic Neovascularization
Interleukin-12
Oxygen
Interleukins
Retinal Neovascularization
Interferon-gamma
Intravitreal Injections
Chemokines
Knockout Mice
Retina
Endothelial Cells
Air
Cytokines
Messenger RNA
Injections

All Science Journal Classification (ASJC) codes

  • General

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Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy. / Zhou, Yedi; Yoshida, Shigeo; Kubo, Yuki; Kobayashi, Yoshiyuki; Nakama, Takahito; Yamaguchi, Muneo; Ishikawa, Keijiro; Nakao, Shintaro; Ikeda, Yasuhiro; Ishibashi, Tatsuro; Sonoda, Koh Hei.

In: Scientific reports, Vol. 6, 28140, 17.06.2016.

Research output: Contribution to journalArticle

Zhou, Yedi ; Yoshida, Shigeo ; Kubo, Yuki ; Kobayashi, Yoshiyuki ; Nakama, Takahito ; Yamaguchi, Muneo ; Ishikawa, Keijiro ; Nakao, Shintaro ; Ikeda, Yasuhiro ; Ishibashi, Tatsuro ; Sonoda, Koh Hei. / Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy. In: Scientific reports. 2016 ; Vol. 6.
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