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ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration

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Item Type:Article
Title:ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration
Creators Name:Zandi, S. and Nakao, S. and Chun, K.H. and Fiorina, P. and Sun, D. and Arita, R. and Zhao, M. and Kim, E. and Schueller, O. and Campbell, S. and Taher, M. and Melhorn, M.I. and Schering, A. and Gatti, F. and Tezza, S. and Xie, F. and Vergani, A. and Yoshida, S. and Ishikawa, K. and Yamaguchi, M. and Sasaki, F. and Schmidt-Ullrich, R. and Hata, Y. and Enaida, H. and Yuzawa, M. and Yokomizo, T. and Kim, Y.B. and Sweetnam, P. and Ishibashi, T. and Hafezi-Moghadam, A.
Abstract:Age is a major risk factor in age-related macular degeneration (AMD), but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK) signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.
Keywords:Aging, Bone Marrow Cells, Cell Differentiation, Cell Polarity, Cultured Cells, Choroid, Choroidal Neovascularization, Cytokines, Inbred C57BL Mice, Macrophages, Macular Degeneration, NF-{kappa} B, {rho}-Associated Kinases, Signal Transduction, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:1173-1186
Date:24 February 2015
Official Publication:https://doi.org/10.1016/j.celrep.2015.01.050
PubMed:View item in PubMed

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