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Norihito Fujita, Shuko Fujita, Nahoko Ogata, Masato Matsuoka, Yuka Okada, Shigeyuki Kon, Toshimitsu Uede, Shizuya Saika; Endogenous Osteopontin Involvement in Laser-Induced Choroidal Neovascularization in Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(13):9310-9315. doi: 10.1167/iovs.10-7050.
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To evaluate the effects of the lack of osteopontin (OPN) and the administration of anti-OPN antibody on inflammation and vascular endothelial growth factor (VEGF) expression in choroidal tissue and on the development of choroidal neovascularization (CNV) after retinal photocoagulation in mice.
CNV was induced in one eye each of 20 C57BL/6-background OPN-deficient mice or 20 wild-type littermates. In another series of experiments, CNV was induced in 40 C57BL/6 mice treated with intraperitoneal administration of 400 μg anti-OPN (SLAYGLR) neutralizing antibody or control IgG. Four laser spots were prepared in each eye. At day 14, the size of the CNV was evaluated by high-resolution angiography with fluorescein isothiocyanate (FITC)-dextran. Six wild-type or six knockout mice also received photocoagulation and processed for histology. mRNA expression of OPN, VEGF, and F4/80 macrophage antigen in laser-irradiated choroidal tissues was analyzed at day 3 in wild-type or knockout mice as well as in wild-type mice treated with anti-OPN antibody or control antibody.
Photocoagulation upregulated OPN expression in choroidal tissue. Histology did not uncover the effects of the lack of OPN on the healing of laser injury in choroid. The lack of OPN or systemic administration of anti-OPN antibody suppressed mRNA expression of VEGF and macrophage invasion in choroidal tissue. FITC-dextran angiography showed that lacking OPN or systemic anti-OPN antibody reduced the size of laser-induced CNV.
OPN is upregulated in laser-irradiated choroidal tissue. Endogenous OPN is required for macrophage inflammation and VEGF expression in choroidal tissue and for CNV development after retinal photocoagulation in mice.
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