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Magali M. Le Goff, Matthew Sutton, Mark Slevin, Martin J. Humphries, Paul N. Bishop; The Vitreous Glycoprotein Opticin Inhibits Extracellular Matrix-driven Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4843.
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Opticin is a glycoprotein associated with the collagen fibrils of the vitreous. The vitreous is normally avascular, but in eye pathologies leading to preretinal neovascularization, collagen fibrils are thought to provide both a physical support and pro-angiogenic stimulation to blood vessels growing into the vitreous. We have shown that in vivo, opticin inhibits blood vessel invasion into the vitreous and here we investigate its mechanism of action.
In vitro endothelial cell (EC) capillary morphogenesis assays were performed in collagen, Matrigel and fibrin matrices under FGF-2 stimulation, in the absence or presence of opticin. ECs were allowed to spread on various ECM ligands including collagen I, II, IV and laminin, opticin was then added to the media; 10 minutes later the cells were fixed and focal adhesions and the actin cytoskeleton were fluorescently labeled. ELISA-based assays were used to study interactions between collagens/laminin, opticin and recombinant α1β1/α2β1 integrins.
Opticin inhibited capillary morphogenesis in both collagen and Matrigel matrices, but not in fibrin gels. In cell spreading assays opticin disrupted EC focal adhesions and their actin cytoskeleton on collagen I, II, IV and laminin leading to rounding up of the cells. However opticin had no effects on ECs spread on fibronectin or vitronectin. Solid phase assays demonstrated that opticin binds strongly to collagen I, II, IV and laminin and this binding inhibits the interaction between these ECM molecules and their cellular receptors, α1β1 and α2β1 integrins.
Here we showed that opticin suppresses collagen and laminin stimulated-angiogenesis by binding directly to these ECM molecules and thereby preventing their interaction with ECs via α1β1/α2β1 integrins.
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