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B. J. Raisler, R. King; Macrophage Infiltration in CCR2 Deficient Mice in OIR Mouse Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4478.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the macrophage response in CCR2 -/- mice in the oxygen induced retinopathy mouse model during the establishment and regression of pre-retinal neovascularization.
Macrophage signaling was measured by bead-array analysis for cytokines (M-CSF, MCP-1, MIP-1alpha and beta) in retinal homogenates at time points through the OIR model. Macrophage infiltration was assessed by in paraffin embedded retinal cross-sections with IHC/IF for F4/80 and CD68. Macrophage numbers were determined by comparative flow cytometry for F4/80+/CD11c- populations between wild-type and CCR2 -/- mice. Lastly macrophage induced apoptosis was measured by staining for activated caspase-3 in retinal cross-sections.
CCR2 -/- mice show elevated levels of MCP-1 relative to their wild-type counterparts, 23% elevation, n=5, p<0.05. M-CSF levels were also elevated at early time points in the OIR model, though the differences were not statistically significant between the groups. Sections from CCR2 -/- mice clearly show macrophages associated with retinal vessels similar to wild-type. Flow cytometry of retinal cells from CCR2 -/- mice and WT during the OIR model showed increased levels of macrophages in the period immediately following return to room air. Apoptosis during the regression of retinal NV is present in both CCR2 -/- and WT mice indicating that functional macrophages may contribute to regression in the signaling deficient mice.
Interestingly, CCR2 -/- mice seem to exhibit a persistant macrophage response despite a lack of signaling through the MCP-1/CCR2 pathway. This is in contrast to MCP-1 -/- mice which have previously been reported to have a reduction in macrophages as well as a delayed regression of pathologic retinal vasculature (Davies, et al, IOVS, 2008). This provocative finding hints at the existence of an alternate receptor for MCP-1 that may be signaling macrophage response in these animals and modulating their neovascular response. Disregulation of macrophage related cytokines may contribute to the differential progression observed between MCP-1 -/- and CCR2 -/- mice in the OIR model.
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