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Hideyasu Oh, Hitoshi Takagi, Chikako Takagi, Kiyoshi Suzuma, Atsushi Otani, Kazuhiro Ishida, Miyo Matsumura, Yuichiro Ogura, Yoshihito Honda; The Potential Angiogenic Role of Macrophages in the Formation of Choroidal Neovascular Membranes. Invest. Ophthalmol. Vis. Sci. 1999;40(9):1891-1898.
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purpose. To investigate the distribution of inflammatory mediators such as
interleukin (IL)-1β and tumor necrosis factor (TNF)-α and
angiogenic cytokines such as vascular endothelial growth factor (VEGF)
and to identify their cellular source in surgically excised choroidal
neovascular membranes (CNVMs) of various origins. methods. Immunoperoxidase staining was performed on paraffin-embedded sections
of 11 surgically excised CNVMs to identify cellular distribution and
localization of cytokines. Immunofluorescent double staining was
performed to detect the cellular source of cytokines. results. Cytokeratin-positive cells were detected in the RPE layer, in stromal
cells, and around neovascular vessels. Macrophages identified by their
cellular marker CD68 showed almost the same distribution as
cytokeratin-positive cells, although they were most prominent in the
stroma. A substantial number of neovascular vessels were also
immunoreactive to IL-1β and TNF-α. Immunofluorescent double
staining revealed that the RPE layers immunopositive for cytokeratin
were also immunopositive for all cytokines, whereas stromal cells
immunostained for CD68 were positive for IL-1β and TNF-α, but not
for vegf. conclusions. These results indicate that IL-1β and TNF-α secreted by macrophages
may promote, at least in part, angiogenesis in CNVMs by stimulating
VEGF production in RPE cells.
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