Expressions of angiopoietins and Tie2 in human choroidal neovascular membranes.
OBJECTIVE
To elucidate the potential role of angiopoietins and the Tie2 system in choroidal neovascularization.


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.
Otani
A
A
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Takagi
H
H
Oh
H
H
Koyama
S
S
Matsumura
M
M
Honda
Y
Y
D000328:Adult; D000368:Aged; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042787:Receptor, TIE-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016228:Endothelial Growth Factors; D005136:Eye Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2