Journal
CELL REPORTS
Volume 10, Issue 7, Pages 1173-1186Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.01.050
Keywords
-
Categories
Funding
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases through Diabetes Complications Consortium [25732-30]
- BrightFocus Foundation
- Malaysian Palm Oil Board
- JSPS KAKENHI [25713057]
- [R01DK083567]
- Grants-in-Aid for Scientific Research [22116001, 15H05897, 22116002, 15H04708, 15H05904] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available