Abstract

Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and Matrigel(TM). We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via α(1)β(1) and α(2)β(1) integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins.

Highlights

  • We demonstrated that the glycoprotein opticin is anti-angiogenic

  • Opticin Inhibits Growth Factor-induced Angiogenesis in Chorioallantoic Membrane (CAM) Assay—This assay was used to determine whether the anti-angiogenic activity of opticin is growth factor-specific

  • In each case, all new vessels converged toward the site of application of growth factor-containing pellets, but if opticin was present in the pellets, the neovascular response was inhibited significantly (Fig. 1, A and B)

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Summary

Background

We demonstrated that the glycoprotein opticin is anti-angiogenic. Here, the underpining mechanism is explored. Results: By binding to collagen, opticin competitively inhibits integrin-mediated endothelial cell adhesion. Conclusion: Opticin inhibits angiogenesis by weakening endothelial cell adhesion to the surrounding extracellular matrix. Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. We discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and MatrigelTM. Anti-angiogenic Activity of Opticin with the integrin-mediated interactions between ECs and collagen and thereby prevents angiogenesis

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