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Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD)

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Abstract

Purpose

Age-related macular degeneration (AMD) is a major cause of progressive and degenerative visual impairment. Although the exact pathogenic mechanism of AMD is still unknown, clinical observations such as the high accumulation of oxidative products and macrophages in retina suggest the importance of oxidative stress and inflammation in AMD.

Methods

Mouse photoreceptor-derived 661 W cells and human ARPE-19 cells were treated with oxidized phospholipids (Ox-PC) or H2O2 to mimic oxidative damage. The effect of monocyte chemoattractant protein 1 (MCP-1) secreted by retina cells on the migration of monocyte macrophage RAW 264.7 cells was determined using transwell chambers and antibody neutralization assay. MCP-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and vascular endothelial growth factor (VEGF) that secreted into supernatant were measured by ELISA and their intracellular expression was detected by qRT-PCR and western blot. Intracellular Ox-PC level was detected by competitive ELISA. The amount of migrated RAW 264.7 cells was counted by flow cytometry.

Results

Oxidative damage by both H2O2 and Ox-PC induced the secretion of MCP-1 in human ARPE-19 and mouse 661 W cells. MCP-1 induced by oxidative damage enhanced the migration ability of macrophage RAW 264.7 cells and the secretion of TNF-α, IL-1β and VEGF, which could be reduced by anti-MCP-1 neutralizing antibodies.

Conclusion

The results indicated that oxidative damage increases intracellular Ox-PC and the secretion of MCP-1 in retina cells. The increased MCP-1 induced by oxidative damage attracts macrophages to retinas, and macrophages release pro-inflammatory factor and promote the process of AMD.

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Correspondence to Zhaojiang Du.

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Funding

The Youth Fund Project of National Natural Science Foundation of China (No. 81100670) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of China provided financial support in the form of research funding. The sponsor had no role in the design or conduct of this research.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Animal experiments

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Zhaojiang Du, Xuemei Wu and Meixia Song contributed equally to this work.

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Du, Z., Wu, X., Song, M. et al. Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD). Graefes Arch Clin Exp Ophthalmol 254, 2469–2476 (2016). https://doi.org/10.1007/s00417-016-3508-6

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  • DOI: https://doi.org/10.1007/s00417-016-3508-6

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