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Atsushi Otani, Hitoshi Takagi, Hideyasu Oh, Shinji Koyama, Miyo Matsumura, Yoshihito Honda; Expressions of Angiopoietins and Tie2 in Human Choroidal Neovascular Membranes. Invest. Ophthalmol. Vis. Sci. 1999;40(9):1912-1920.
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purpose. To elucidate the potential role of angiopoietins and the Tie2 system in
methods. Surgically excised choroidal neovascular membranes (CNVMs) were
obtained at vitrectomy from five eyes with age-related macular
degeneration, three eyes with idiopathic neovascular maculopathy, and
two eyes had degenerative myopia and two eyes had angioid
streaks. Light microscopic immunohistochemistry was performed to detect
cytokines such as vascular endothelial growth factor (VEGF), Ang1, and
Ang2 and cellular components such as retinal pigment epithelial (RPE)
cells, macrophages, and endothelial cells. Immunofluorescent double
staining using confocal microscopy was performed to identify the cell
types that secrete specific cytokines.
results. Ang1 and Ang2 were positive in all surgically excised CNVMs, regardless
of the primary disease. Double staining revealed that many of the
cytokeratin, CD68 and factor VIII positive cells also had Ang1 and Ang2
immunoreactivities. In contrast to Ang1, Ang2 immunoreactivity tends to
be higher in the highly vascularized regions of many CNVMs, and the
localization was very similar to that of VEGF staining. Almost all
vascular structures had prominent immunoreactivity for Tie2, which was
confirmed by double staining for Tie2 and factor VIII. Tie2
immunoreactivity was also observed in the RPE monolayer and in
pigmented, polygonal, and fibroblast-like cells in the stroma.
conclusions. Present findings that Ang2 and VEGF are co-upregulated and that Tie2 is
expressed in a variety of cell types in CNVMs further support a crucial
role of the interaction between VEGF and Ang2 in pathologic
angiogenesis of CNVM formation.
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