Receptor‑selective interleukin‑4 mutein attenuates laser‑induced choroidal neovascularization through the regulation of macrophage polarization in mice

Gao,Limo; Jiang,Wenmin; Liu,Haiying; Chen,Zhiheng; Lin,Yanhui

doi:10.3892/etm.2021.10801

Receptor‑selective interleukin‑4 mutein attenuates laser‑induced choroidal neovascularization through the regulation of macrophage polarization in mice

Authors:
- Limo Gao
- Wenmin Jiang
- Haiying Liu
- Zhiheng Chen
- Yanhui Lin
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Affiliations: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Hunan University of Finance and Economics, Changsha, Hunan 410205, P.R. China, Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 27, 2021 https://doi.org/10.3892/etm.2021.10801
Article Number: 1367
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophage polarization has been recognized as an important inflammatory regulator in choroidal neovascularization (CNV). However, the mechanisms regulating macrophage activation and polarization, as well as their effects on angiogenesis and CNV, have not yet been elucidated. IL‑4 is implicated in macrophage activation and exerts different functions in various diseases through several receptors. In the current study, the effect of IL‑4 muteins on CNV was investigated in vivo. CNV was induced by laser coagulation in wild type mice. IL‑4 muteins were recombined into adenoviruses and injected into mice via the tail vein. To evaluate CNV, fluorescein fundus angiography and optical coherence tomography were performed on day 7 after coagulation. Quantitative PCR, western blotting and immunofluorescence staining were used to assess the levels of inflammatory markers. AdIL‑4/Q116E, an adenovirus‑expressed recombinant IL‑4 mutein, selectively activated macrophages, alleviated laser‑induced CNV in mice with reduced expression of M2 macrophages and increased the expression of M1 macrophages. Furthermore, the expression of monocyte to macrophage differentiation‑associated and delta‑like 4 (Dll4) in CNV lesions was upregulated. Employing AdIL‑4/Q116E, a IL‑4RI‑selective mutein, may serve as a new strategy for CNV therapy. Moreover, the results indicated that Dll4 signaling served an important role in the regulation of macrophage polarization.

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