| Budget Amount *help |
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2012: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2011: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Research Abstract |
The purpose of this study is to clarify regulatory mechanism of macrophages in choroidal neovascular diseases. We show that IL-27, a regulatory cytokine, inhibited VEGFA production in macrophage in vitro. IL-27 also suppressed CNV by VEGFA reduction but not macrophage recruitment in vivo. M2 macrophage (M2) is reported as a source of VEGFA in CNV, indicating that IL-27 might regulate M2 differentiation and/or activation in CNV. Next, we focused on HSP70, an endogenous ligand for Toll-like receptor (TLR) 4/TLR2. HSP70, located in the cytosol and the nucleus of various kinds of cells, is released in response to cellular stress. Although M2 promotes cancer-associated fibrosis by activation of TLR4 signaling, subretinal fibrosis was suppressed by intraocular injection of HSP70 through induction of IL-10, an anti-inflammatory cytokine, via TLR4/TLR2 signaling. The induction of IL-10 was dependent on RPE, but not macrophages, suggesting that RPE is also important for the regulation.
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