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Mauricio Rosenfeld, Faith H. Barnett, Edith Aguilar, Martin Friedlander; Neovascular tufts are perfused vascular structures formed in part by macrophage/microglia cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2228.
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© 2017 Association for Research in Vision and Ophthalmology.
Macrophages form a perfused vascular network under hypoxic conditions in both the subcutaneous matrigel angiogenesis model and in mouse melanoma tumor models. In the subcutaneous tumor model, macrophages form perfused tuft-like structures within the tumor associated angiogenic vasculature. To determine if a similar process occurs in the retina, we studied a murine model of retinopathy of prematurity (OIR). In this model, newly formed vessels in the central retina of the neonatal mouse regress when exposed to high oxygen (vaso-obliterated area, VO). Upon return to normal oxygen conditions, neovascular tufts are formed in the retina in areas of the remaining superficial plexus. Macrophages/microglia (Mac/Mg) are known to be closely associated with these structures. To determine if the Mac/Mg were juxtaposed or structurally involved in the neovascular structures, we studied the role of Mac/Mg in neovascular regions in the OIR model.
Using the oxygen-induced retinopathy (OIR) model, P7-P12 mice were subjected to 75% oxygen. To detect functional vasculature, P14-P17 pups were infused with variable molecular weight fluorescent compounds (3 -2 X 106kd) by intracardiac perfusion (n=6-20 eyes/group). Whole mounts were prepared of fixed retinas, immunostained for both Mac/Mg and endothelial markers and analyzed by high resolution confocal microscopy. The images were reconstructed into 3-D images using Imaris software.
Neovascular tufts are multinucleated structures projecting into the vitreous. The tufts are attached to the superficial plexus by a stalk. At P17, the stalk and the tufts are formed from cells expressing CD11B and IBA1 (both being Mac/Mg markers). The neovascular tufts are perfused by intravenously injected dyes.
Cells expressing the macrophage markers CD11B and IBA1 are structural components of neovascular tufts in the OIR model. The tufts are perfused by systemically injected dye demonstrating a functional connection to the superficial vascular plexus in the neonatal mouse retina after OIR. Mac/Mg are structurally involved in the formation of perfused, multinucleated tufts in both tumors and pathological angiogenesis in the eye.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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