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K Arango, DG Espinosa, DC Monroy, E Hernandez, JM Legra, KG Csaky, SW Cousins; Macrophage Depletion Diminishes Lesion Size and Severity in Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1294.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Innate immunity, especially macrophage recruitment to the choroid by cytokines or deposits produced by the RPE, has been proposed to contribute to AMD pathogenesis. Macrophages have been observed to insert membrane porocesses into drusen and to infiltrate into choroidal neovascularization (CNV). We sought to determine if treatment with clodronate liposomes (Cl2MDP-lip), which produces depletion of blood monocytes and lymph node macrophages, influences the severity of neovascularization in a mouse model of laser induced choroidal neovascularization (CNV). Methods: Laser induced CNV was performed in male 9 month-old C57BL/6 mice. Macrophages were depleted by use of Cl2MDP-lip intraperitoneally and subcutaneously 48 and 24 hours before, as well as every 2 days after, laser injury. Controls recieved either saline or empty liposomes. Blood monocyte depletion was documented by flow cytometry. Two weeks after laser, mice were injected intravenously with fluorescinated dextran. The right eyes were removed and prepared for flatmount analysis of CNV surface area (in relative disc areas or DA), vascularity (relative fluorescence), and cellularity (propidium iodide stain). Then, the mice were perfused with 10% formaldehyde, and the left eyes were removed for histopathology. The mean of the various parameters for four CNV per eye were calculated. Results: Flow cytometry confirmed the effective depletion of blood monocytes by Cl2MDP-lip treated mice. Compared to controls, macrophage depleted mice demonstrated significant reduction in size of CNV (2.3±0.2 DA v 1.5±0.1 DA, p<0.01). Mean vascularity and cellularity of CNV were slightly less in the treated group. Histopathology also revealed that CNV were smaller in diameter and thickness in the macrophage-depleted group. An inverse correlation was observed between smaller CNV size and increased percentage of residual blood monocytes at the time of analysis. Conclusions: Macrophage depletion using Cl2MDP-lip reduces the size, and to a lesser extent, cellularity and vascularity of CNV. This observation supports the hypothesis that macrophages contribute to the induction and formation of CNV.
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