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OW Kwon, SH Lee, BY Ahn, WI Yoo, YS You, DS Kim; The Novel Angiogenic Inhibitor Saxatilin Reduce Ocular Neovascularization Elicited by bFGF and Hyperoxia . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3716.
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Purpose: The purpose of the present study was to explore the potential of saxatilin in the treatment of ocular neovascularization. In the previous studies, anti-angiogenic activity of this polypeptide was determined in cultured primary human umbilical vein endothelial cell proliferation induced by bFGF. Saxatilin is a novel disintegrin derived from venom of Gloydius saxatilis, potently inhibited human platelet aggregation caused by adenosine diphosphate (ADP) through the blockade of fibrinogen binding to platelet glycoprotein IIb/IIIa. This protein is a single-chain polypeptide composed of 73 amino acids including the tripeptide sequence Arg-Gly-Asp, a proposed recognition site of adhesive proteins. Methods: We demonstrated that saxatilin is an inhibitor of angiogenesis induced by bFGF(650ng)in rabbit cornea. And we investigated whether saxatilin could inhibit retinal neovascularization on oxygen induced retinopathy (OIR) mouse model. Retinal neovascularization was induced in newborn mice pups by exposure to hyperoxia (75% oxygen / five days) and then normoxia. Saxatilin was intraperitonealy injected into the mouse model (0.1-10 mg/kg/day for five days). The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused or ADPase stained retinal flat mounts. Results: Treatment with saxatilin revealed a significant reduction of corneal vessel growth in animals with bFGF-induced corneal vascularization, compared with control groups treatment with vehicle. And, the oxygen-induced retinopathy animal model showed an retinal neovascularization, haemorrhage, and blood vessel tortuosity. Intraperitoneal injection of saxatilin resulted in fewer neovascular tufts and pre-retinal vascular cells than in control mouse with vehicle injection. Conclusion: These results suggest that saxatilin, angiogenic inhibitor could have therapeutic effects on ocular neovascular diseases.
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