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Jin Zhao, Takayuki Nagasaki; Macrophages, Pericytes, and Smooth Muscle Cells in Corneal Angiogenesis and Regression. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4500. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous studies showed that: 1) there are abundant macrophages in the vicinity of growing blood vessel fronts; 2) a periendothelial “pale” cell of unknown identity was found in an ML-9 induced angiogenesis model. The aim of this study is to examine the participation of macrophages, pericytes, and smooth muscle cells (SMCs) during pathological corneal vascular growth and subsequent regression.
A suture-induced angiogenesis model was used in the mouse eye. Vascular regression was studied after suture removal. Vasculature was monitored by angiography in vivo and analyzed by histology with transmission electron microscopy (TEM) and whole-mount immunostaining, using CD31 for endothelial cells, F4/80 for macrophages, NG2 for pericytes, and α-smooth muscle actin for SMCs.
Following suture placement in the cornea, capillary vessels grew toward the suture at a rate of about 150 µm/day. TEM revealed the presence of “pale” cells with sparse cytoplasmic organelles near vessel tips and also at a branching point where they shared basement membranes with endothelial cells, suggesting a role in capillary branching or anastomosis. Varying lengths of growing capillary tips, ranging from 0 to 150 µm from the growth front, were free from pericytes. The largest distance is the length of two endothelial cells, or the distance that capillary grows in about 1 day, indicating that all growing capillaries older than one day were totally decorated with pericytes. SMCs were never found at the first 50 µm of capillary tips, and some vessels had no SMCs up to 300 µm from the growth front. These are the distances that extend beyond the first branching point of growing vessels. Some macrophages appeared to be in direct contact with endothelial cells in the pericyte-free zone. During vascular regression, remaining blood vessels were fully covered by pericytes and SMCs while abundant macrophages were present near them. Some macrophages maintained ghost shape of disintegrated blood vessels.
A growth front of capillary blood vessels is free from pericytes and SMCs for a maximum of one day for pericytes and two days for SMCs. Some macrophages in this area are in direct contact to endothelial cells. As such, this is a dynamic zone that endothelial tip cells incorporate macrophages, pericytes, and SMCs, which may be amenable to an intervention for controlling pathological vascular growth.
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