Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway - PubMed (original) (raw)

doi: 10.1111/jpi.12660. Epub 2020 May 15.

Kaixuan Cui 1, Jia Li 1, Xiaoyu Tang 1, Jianqiang Lin 1, Xi Lu 1, Rong Huang 1, Boyu Yang 1, Yuxun Shi 1, Dan Ye 1, Jingjing Huang 1, Shanshan Yu 1, Xiaoling Liang 1

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Melatonin attenuates choroidal neovascularization by regulating macrophage/microglia polarization via inhibition of RhoA/ROCK signaling pathway

Yue Xu et al. J Pineal Res. 2020 Aug.

Abstract

Choroidal neovascularization (CNV) is an important characteristic of advanced wet age-related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti-inflammation, and anti-angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser-induced mouse CNV model. Additionally, the results also show that the melatonin-treated retinal microglia in the laser-induced mice exhibited enhanced expression of M1-type markers, such as iNOS, CCL-3, CCL-5, and TNF-α, as well as decreased production of M2-type markers, such as Arg-1, Fizz-1, IL-10, YM-1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro-angiogenic M2 phenotype to anti-angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.

Keywords: RhoA/ROCK signaling pathway; age-related macular degeneration; choroidal neovascularization; macrophage; melatonin; microglia; polarization.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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