Abstract
Purpose: :
Recently, the importance of inflammation and immunology activation has been highlighted in the pathology of choroidal neovascularization (CNV), especially the monocyte and macrophages. Depletion of macrophages has been shown to reduce severity of laser-induced CNV in early stage. This study investigates the effects of macrophages on laser-induced mice CNV throughout a long term after systemically depleting monocyte-macrophages.
Methods: :
CNV was established using laser photocoagulation. To systemically deplete monocyte-macrophages, mice were injected liposomal clodronate (Cl2MDP-lip) intraperitoneally at 72, 24 hours before and after laser injury. Meanwhile,two control groups receiving no injection or PBS-liposome intraperitoneal injection were also set. CNV incidence was analyzed by fundus fluorescein angiography. Quantitative analysis of CNV was done with paraffin embedded sections by measuring cell number, the maximum thickness and the area of CNV at various time following laser photocoagulation. Besides, macrophages, endothelial cells and VEGF proteins were detected by immunofluorescein staining on day 3 after laser injury.
Results: :
Three groups showed similar CNV incidence. Compared to the controls, Cl2MDP-lip administered mice had significant less cells in the lesions on day 3 and decreased thickness and area of CNV on day 14 after laser injury(P<0.05). On day 28, the area remained smaller (P<0.05), while the thickness became similar(P>0.05). On day 56, no differences could be observed. The two control groups had similar values. Compared to mice receiving no injection, Cl2DMP-lip mice had less macrophages infiltration in the lesion on day 3 (P<0.001). The number of endothelial cells and the expression of VEGF protein also seemed decreased.
Conclusions: :
Depletion of macrophages although could not stop laser-induced CNV formation, may reduce the severity of CNV in early stage and the effect could be maintained throughout the regression stage. The effect may be partly attributed to the reduction of infiltration and proliferation of endothelial cells and expression of VEGF protein caused by the depletion of macrophages.
Keywords: choroid: neovascularization • inflammation • age-related macular degeneration