| Authors |
Zandi S, Nakao S, Chun KH, Fiorina P, Sun D, Arita R, Zhao M, Kim E, Schueller
O, Campbell S, Taher M, Melhorn MI, Schering A, Gatti F, Tezza S, Xie F, Vergani
A, Yoshida S, Ishikawa K, Yamaguchi M, Sasaki F, Schmidt-Ullrich R, Hata Y,
Enaida H, Yuzawa M, Yokomizo T, Kim YB, Sweetnam P, Ishibashi T, Hafezi-Moghadam
A
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| Submitted By |
Ali Hafezi-Moghadam on 3/4/2015 |
| Status |
Published |
| Journal |
Cell reports |
| Year |
2015 |
| Date Published |
2/24/2015 |
| Volume : Pages |
10 : 1173 - 1186 |
| PubMed Reference |
|
| 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.
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