Endostatin prevents laser-induced CNV in mice
66 and is reduced in the choroid of AMD patients compared to age-matched mates.
67 Angiostatin has the potential to inhibit the proliferation, migration, differentiation, and tube formation of endothelial cells in vitro.
68 Annexin, angiomotin, integrin ανβ3, and c-met are cell-surface proteins that bind angiostatin.
69 The binding of angiostatin to tissue plasminogen activator results in a reduced cellular migration and invasion.
70 Angiostatin binds to subunits of ATP synthase on the cell surface of endothelial cells,
71 targets the Krebs cycle in mitochondria,
72 and binds to integrin ανβ3, which is probably necessary for angiogenesis. Furthermore, angiostatin inhibits the response of stimulated endothelial cells and smooth muscle cells to hepatocyte growth factor by interrupting G2/M transition during the cell cycle,
73 competitively antagonizes VEGF- and/or basic fibroblast growth factor–induced signaling (linked to AMD),
74 and strongly blocks the neovascularization and growth of tumor metastases.
20 The present findings showed that angiostatin is expressed in the GCL, IPL, and OPL throughout the neuroretina. To our knowledge, the present study is the first to demonstrate regional differences in angiostatin expression in the primate retina. Other studies have found retinal effects after intraocular angiostatin administration. The systemic administration of angiostatin completely prevented retinal neovascularization in a mouse model of oxygen-induced retinopathy.
28 Recombinant angiostatin successfully suppressed experimental angiogenesis without signs of toxic effects to the retina.
75 A clinical phase I dose escalation study is reported with endostatin and angiostatin subretinal injections in advanced neovascular CNV (reviewed in Ref. 76), however, with no clinical results available.