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Takahiro Yamawaki, Jun Yamada, Eiko Ito, Shigeru Kinoshita, Chie Sotozono, Jyunji Hamuro; Inflammatory vicious cycle between retinal pigment epithelium (RPE) and macrophages reduces the phagocytic function of RPE. Invest. Ophthalmol. Vis. Sci. 2016;57(12):481. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Age-relate macular degeneration (AMD) is partly caused by chronic inflammation. To date, no reports have described the contribution of the interaction of RPE with macrophages (Mps) in degeneration of RPE. The purpose of this study is to investigate the formation of a vicious inflammatory cycle between Mps and RPE, and its impact upon phagocytosis of photoreceptor outer segments (POS) by RPE.
Mps semi-purified as adherent peritoneal cells and primary RPE were taken from C57BL/6 mice, then co-cultured with or without LPS or TNFα stimulation. VEGF, MCP-1, and IL-6 in the supernatant were quantified by enzyme-linked immunosorbent assay (ELISA). To investigate the effect of Mps polarization, Mps cultured with glutathione ethyl ester (GSH-OEt) were also used. RPE, pre-exposed with supernatant of co-culture of RPE with Mps were investigated for the amount of POS phagocytosed by RPE using Image J softwear®.
The production of VEGF, MCP-1 and IL-6 were synergistically increased when primary Mps and RPE were co-cultured compared with either Mps or RPE alone. This synergistic effect was far increased in the presence of LPS or TNFα stimulation. Moreover, the synergistic augmented production of these three cytokines were reduced by co-culture with Mps polarized into M1. The reduction of TNFα production by Mps was greatly reduced by co-culture with RPE. Of note, co-culture derived supernatant reduced phagocytic activity of POS by RPE than those of RPEs exposed to the culture supernatant from RPE or Mps alone, indicating the accelerated degeneration of RPE by vicious inflammatory cycle between Mps and RPE. The effect may be induced by Mps polarized to M2.
Inflammatory vicious cycle between Mps and RPE may contribute to degenerate the function of PRE, namely the reduction of phagocytosis of POS by RPE.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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