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T. Yoshida, J. Shen, C. Seidel, S. Hackett, R. Lang, P. A. Campochiaro; Macrophage Ablation Suppresses Laser-Induced Choroidal Neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2009;50(13):1174.
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The purpose of this study was to explore the role of macrophages in the development of CNV.
The size of CNV at sites of Bruch’s membrane rupture with laser was evaluated in transgenic mice in which the CD11b promoter drives expression of diphtheria toxin receptor (DTR) selectively on macrophages with and without injection of diphtheria toxin (DT).
Intraperitoneal injection of 25 ng/g DT in CD11b-DTR transgenic mice resulted in a marked reduction in F4/80-positive macrophages in the RPE/choroid and retina and a significant reduction in area of CNV at Bruch’s membrane rupture sites. Compared to untreated CD11b-DTR mice (n=51) in which the mean (± SEM) area of CNV was 0.01212±0.00282 mm2, it was significantly less in CD11bDTR mice in which macrophages had been ablated by injection of DT (0.00591±0.0008 mm2, n=39). Real time PCR of total RNA isolated from the RPE/choroid of 5 untreated and 5 DT-treated CD11b-DTR mice, showed that mRNA for macrophage inflammatory protein-1, monocyte chemoattractant protein-1, interleukin-1β, and vascular endothelial growth factor were significantly reduced.
Severe reduction of macrophages in the retina and choroid suppresses the development of CNV after rupture of Bruch’s membrane.
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