IOVS Arteriosclerosis, Thrombosis, and Vascular Biology
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(Investigative Ophthalmology and Visual Science. 1999;40:1891-1898.)
© 1999 by The Association for Research in Vision and Ophthalmology, Inc.

The Potential Angiogenic Role of Macrophages in the Formation of Choroidal Neovascular Membranes

Hideyasu Oh1, Hitoshi Takagi1, Chikako Takagi1, Kiyoshi Suzuma1, Atsushi Otani1, Kazuhiro Ishida1, Miyo Matsumura1, Yuichiro Ogura2 and Yoshihito Honda1

1 From the Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University; and the 2 Department of Ophthalmology, Nagoya City University Medical School, Japan.

Abstract

PURPOSE. To investigate the distribution of inflammatory mediators such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-{alpha} 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-1ß and TNF-{alpha}. 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-1ß and TNF-{alpha}, but not for VEGF. CONCLUSIONS. These results indicate that IL-1ß and TNF-{alpha} secreted by macrophages may promote, at least in part, angiogenesis in CNVMs by stimulating VEGF production in RPE cells.




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