Premium
Endogenous endostatin inhibits choroidal neovascularization
Author(s) -
Marneros Alexander G.,
She Haicheng,
Zambarakji Hadi,
Hashizume Hiroya,
Connolly Edward J.,
Kim Ivana,
Gragoudas Evangelos S.,
Miller Joan W.,
Olsen Bjorn R.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8422com
Subject(s) - endostatin , choroidal neovascularization , choroid , angiogenesis , macular degeneration , medicine , endogeny , pathogenesis , in vivo , pathology , immunology , retina , biology , endocrinology , cancer research , ophthalmology , neuroscience , genetics
Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antian‐ giogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age‐related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endosta‐ tin and in control mice. CNV lesions in mutant mice were ~ 3‐fold larger than in control mice and showed increased vascular leakage. These differences were independent of age‐related changes at the choroid‐ retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin‐deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions.— Marneros, A. G., She, H., Zambarakji, H., Hashizume, H., Connolly, E. J., Kim, I., Gragoudas, E. S., Miller, J. W., Olsen, B. R. Endogenous endostatin inhibits choroidal neovascularization. FASEB J . 21, 3809–3818 (2007)