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B.–Y. Ahn, Y. You, W. You, O.–W. Kwon, D. Kim; A New Functional Role of Cyclic Rgd Polypeptide as the Angiopoietin–1 Inducer That Triggers Normalization of Retinal Vasculature in Premature Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):144.
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As the alternative therapy for neovascular disease in retina, attention is taken to a use of Angiopoietin–1 (Ang–1), because it major plays a role in stabilizing blood vessel. However, although the evidence indicates that Ang–1 could be relevant to therapeutic angiogenesis, some clinical limitations must be addressed. Ang–1 is difficult to purify in a consistently active form and it contains long N–terminal domains, rendering it insoluble. This study was aimed to investigate a new functional effect of cyclic RGD polypeptide (cycRGD motif), which could induce the Ang–1.
To evaluate the Ang–1 inducing activity of cycRGD motif, western blotting of FAK and Ang–1 was used in 293T and Sarcoma cells. The effect of cycRGD motif was also investigated by oxygen–induced retinopathy (OIR) and VEGF–induced cornea micropocket in the mouse.
cycRGD motif appeared to induce FAK overexpression and phosphorylation, which might be to the increase of cell migration and amount of Ang–1 increased in cell culture medium treated with more than 1µM of cycRGD motif. The mouse treated with cycRGD motif (10 µg/kg, 100 µg/kg) had significantly less oxygen–induced retinal neovascularization and formed near normal retinal vessel network. It is suggesting that cycRGD motif protected the vasculature against leakage and maintained the blood vessel structures during the early stages of neonatal mouse with OIR. And it also observed in mircopocket assayIn the cornea micropocket assay, after daily intraperitoneal injection of 10 ug/kg of cycRGD motif promoted significantly neovascularity compared with VEGF only group. Fluorescent microscopic findings demonstrated enhanced length of vessel and vascular network maturation.
This study showed that Ang–1 inducing effect of cycRGD motif help oxygen damaged retinal vessel to mature vessel network without fibrosis. Therefore, cycRGD motif may be used as a drug for need of vessel normal maturation and stabilization on therapy of eye related diseases as ROP and DR. diabetic retinopathy (DMR).
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