Purchase this article with an account.
M. M. Le Goff, M. Sutton, A. Siewert, D. Ruiz, P. Scott, P. N. Bishop; The Leucine-Rich Repeat Domain of Opticin Confers Its Anti-Angiogenic Activity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2936.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The glycoprotein opticin is found in the vitreous and is a member of the small leucine-rich repeat proteins (SLRP) family. Previously we have demonstrated that opticin inhibits preretinal neovascularisation using the mouse oxygen-induced retinopathy model and shown that it inhibits endothelial cell (EC) network formation in 3D matrices of collagen or MatrigelTM. During angiogenesis matrix metalloproteinases (MMPs) including MMP2 and MMP9 are overexpressed, so we determined whether opticin is sensitive to MMP digestion and then investigated the anti-angiogenic properties of opticin fragments.
Opticin was digested with MMP2 or MMP9 and the resultant fragments were analysed by electrophoresis, N-terminal sequencing and mass spectrometry. In vitro capillary networks were formed in 3D collagen gels using FGF2 stimulated ECs alone or in the presence of full-length opticin, a bacterially-expressed N-terminal fragment of opticin, or in co-culture with 293 cells expressing the leucine-rich repeat (LRR) domain of opticin.
Digestion of opticin with MMP2 or MMP9 cleaved opticin at the junction between its LRR domain and the N-terminal part of the molecule. Full-length opticin and the LRR domain of opticin inhibited capillary morphogenesis in the 3D assays. The N-terminal fragment of opticin did not inhibit capillary morphogenesis.
MMP2 and MMP9 can cleave opticin. This cleavage produces an LRR domain that retains anti-angiogenic properties.
This PDF is available to Subscribers Only