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M. Tokoro, M. Nozaki, M. Ashikari, M. Itaya, Y. Ogura; Osteopontin Blockade Suppresses Laser-Induced Choroidal Neovascularization in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1165.
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Osteopontin (OPN) is a chemokine like phospholyrated glycoprotein. OPN is involved in a number of physiologic and pathologic events including inflammation, tumor genesis and wound healing, and has been considered as a potential therapeutic target for rheumatoid arthritis and anticancer therapy.The purpose of this study was to evaluate the expression of OPN in mice after laser injury, and to determine whether OPN blockade can suppress laser-induced CNV.
CNV was induced by laser injury in C57BL/6J mice, and CNV areas were measured 7 days later by confocal evaluation of Griffonia simplicifolia Isolectin B4 staining of RPE-choroid flatmounts. Anti-Osteopontin antibody (Ab) or PBS (control) was injected into the vitreous following laser injury. The level of OPN was quantified by ELISA on day 0, 1, 3, 5 and 7 days after laser injury. The immunohistochemical study was also performed to determine the expression of OPN in mice after laser injury.
The mean OPN level in the sensory retina significantly increased 1 day after laser injury (p=0.0137) and in the RPE-choroid significantly increased on day 1 and day 3 after laser injury (p=0.0015, p=0.006, respectively). By immunohistochemical staining, OPN was co-localized with infiltrated macrophages after laser injury. OPN Abs suppressed CNV area in dose-dependent manner compared with PBS injected mice. (PBS group 35662.0±19008.6 µm2, OPN 0.01µg group 24954.8±11819.1 µm2, OPN 0.1µg group 12985.7± 6647.3 µm2; p=0.015, p<0.0001, respectively).
Collectively these findings demonstrate that OPN participated in the pathogenesis of CNV. OPN blockade may be considered further therapeutic potential for AMD.
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