Expression of endostatin in human choroidal neovascular membranes secondary to age-related macular degeneration.
Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for its antiangiogenic activity. The aim of this study was to investigate the expression of endostatin in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD) with regard to vascularization and proliferative activity. An interventional case series of 36 patients who underwent removal of CNV were retrospectively investigated. Thirty-six CNV were analyzed by light microscopic immunohistochemistry for the expression of CD34 (endothelial cells, EC), CD105 (activated EC), Ki-67 (cell proliferation), Cytokeratin 18 (epithelial cells), VEGF (vascular endothelial growth factor), E-selectin and endostatin. Donor eyes (n=7) including one with AMD were used as controls. Endostatin immunoreactivity was present in choroidal vessels of five as well as in the retinal pigment epithelium (RPE)-Bruch's membrane complex of two donor eyes without AMD. In one eye with AMD, endostatin was detected in RPE, Bruch's membrane and choroidal vessels. Ninety-two percent (33/36) of CNV disclosed endostatin staining. RPE-Bruch's membrane complex, choroidal vessels and stroma were positive in 50% (18/36), 72% (26/36), and 78% (28/36) of the membranes, respectively. Both control eyes and CNV expressed all the investigated markers except E-selectin being positive only in membranes. Endostatin, an endogenous angiogenesis inhibitor, is expressed in CNV and its therapeutic up-regulation may be a new strategy in the treatment of neovascular AMD.
Tatar
Olcay
O
University Eye Clinic at the Centre for Ophthalmology of the Eberhard-Karls-University Tübingen, Schleichstrasse 12-15, 72076 Tuebingen, Germany.
Shinoda
Kei
K
Adam
Annemarie
A
Rohrbach
Jens Martin
JM
Lucke
Klaus
K
Henke-Fahle
Sigrid
S
Bartz-Schmidt
Karl Ulrich
KU
Grisanti
Salvatore
S
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D016570:Bruch Membrane / Q000737:chemistry; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002829:Choroid / Q000737:chemistry*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism*; D019040:E-Selectin / Q000032:analysis; D000071063:Endoglin; D043169:Endostatins / Q000032:analysis*; D042783:Endothelial Cells / Q000737:chemistry; D005136:Eye Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007633:Keratins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008268:Macular Degeneration / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000032:analysis; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D015703:Antigens, CD; D018952:Antigens, CD34; D019040:E-Selectin; C064206:ENG protein, human; D000071063:Endoglin; D043169:Endostatins; D005136:Eye Proteins; D019394:Ki-67 Antigen; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D007633:Keratins