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A.–K.B. Maier, N. Kociok, G. Zahn, R. Stragies, P.S. Muether, A.M. Joussen; Modulation of Hypoxia Induced Neovascularization by JSM 6427, an Integrin 5ß1 Inhibiting Molecule . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1752.
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Integrin proteins are adhesion receptors which play a critical role in development and stabilization of vasculature. Especially, integrin α5ß1, a fibronectin receptor, is involved in different steps of the angiogenic process including endothelial cell migration and proliferation. Our objective was to investigate the effect of a single intravitreal injection of JSM 6427, an integrin α5ß1 inhibiting molecule, on the development of retinal vascular system using the mouse model of oxygen induced retinopathy (OIR).
C57BL/C6 mice were exposed to 75% oxygen from postnatal day 7 (P7) to day 12 (P12) and then mice were returned to room air. On day 14 (P14) mice were treated by an intravitreal injection of JSM 6427 in one eye and by a control substance in the fellow eye. On P17 the retinal vasculature was visualized by perfusion of the mice with fluorescein coupled concanavalin A. Density slicing was used to quantify vascular and avascular area, neovascular blood vessel tufts and leakage.
The single intravitreal injection of JSM 6427 resulted in a significant reduction of the vascularized area in comparison to the intravitreal injection of the vehicle (0.24 ± 0,06 vs. 0.18 ± 0,03 (p = 0.024)). Similarly, the avascular area increased significantly (0.25 ± 0,05 vs. 0.19 ± 0,08 (p = 0.041)). Results of the intravitreal injection of the vehicle and of the oxygen treatment only were not significant different.
A single intravitreal injection of a α5ß1 inhibiting molecule, JSM 6427, is able to reduce angiogenesis in a mouse model of oxygen induced retinopathy. These results suggest an essential role of integrin α5ß1 in the development and maturing of the retinal vasculature in vivo and emphasize that integrin α5ß1 is possibly a potential target for treatment in the retinopathy of prematurity (ROP).
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