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Kunbei Lai, Li Xu, Chenjin Jin, Kaili Wu, Zhen Tian, Chuangxin Huang, Xiaojing Zhong, Haiyun Ye; Technetium-99 Conjugated with Methylene Diphosphonate (99Tc-MDP) Inhibits Experimental Choroidal Neovascularization In Vivo and VEGF-Induced Cell Migration and Tube Formation In Vitro. Invest. Ophthalmol. Vis. Sci. 2011;52(8):5702-5712. doi: 10.1167/iovs.10-6370.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of 99Tc-MDP, a decay product of 99mTc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms.
C57BL/6J mice were used to induce CNV by laser photocoagulation. 99Tc-MDP at the doses of 0.5 × 10−1, 1 × 10−1, and 2 × 10−1 μg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of 99Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of 99Tc-MDP was evaluated in vivo and in vitro.
Areas of CNV were significantly suppressed by 99Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: 99Tc-MDP treatment of 0.5 × 10−1 μg/kg (5698.60 ± 1037.70 μm2), 1 × 10−1 μg/kg (3678.34 ± 1328.18 μm2), and 2 × 10−1 μg/kg (2365.78 ± 923.80 μm2) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 μm2; P < 0.001). 99Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. 99Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells.
Anti-inflammatory treatment with 99Tc-MDP has therapeutic potential for CNV-related diseases.
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