| Literature DB >> 25704819 |
Souska Zandi1, Shintaro Nakao2, Kwang-Hoon Chun3, Paolo Fiorina4, Dawei Sun5, Ryoichi Arita6, Ming Zhao7, Enoch Kim8, Olivier Schueller8, Stewart Campbell8, Mahdi Taher9, Mark Ivan Melhorn9, Alexander Schering9, Francesca Gatti4, Sara Tezza4, Fang Xie5, Andrea Vergani4, Shigeo Yoshida6, Keijiro Ishikawa6, Muneo Yamaguchi6, Fumiyuki Sasaki10, Ruth Schmidt-Ullrich11, Yasuaki Hata6, Hiroshi Enaida6, Mitsuko Yuzawa12, Takehiko Yokomizo10, Young-Bum Kim13, Paul Sweetnam8, Tatsuro Ishibashi6, Ali Hafezi-Moghadam14.
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.Entities:
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Year: 2015 PMID： 25704819 PMCID： PMC5219927 DOI： 10.1016/j.celrep.2015.01.050
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423