The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes.
OBJECTIVE
To investigate the distribution of inflammatory mediators such as interleukin (IL)-1beta 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-1beta 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-1beta and TNF-alpha, but not for VEGF.


CONCLUSIONS
These results indicate that IL-1beta and TNF-alpha secreted by macrophages may promote, at least in part, angiogenesis in CNVMs by stimulating VEGF production in RPE cells.
Oh
H
H
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
Takagi
H
H
Takagi
C
C
Suzuma
K
K
Otani
A
A
Ishida
K
K
Matsumura
M
M
Ogura
Y
Y
Honda
Y
Y
D000328:Adult; D000368:Aged; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007375:Interleukin-1; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors