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T. Hisatomi, S. Nakao, K. Noda, T. Nakazawa, L. Almulki, Y. Ito, H. She, T. Ishibashi, A. Hafezi-Moghadam, J. W. Miller; Characterization of the Laser-Induced Choroidal Neovascularization in Apoptosis Modified Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):517.
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Laser-injury choroidal neovascularization (CNV) in mice, rats and primates models angiogenic diseases such as age-related macular degeneration. In CNV, robust infiltration of inflammatory cells and endothelial cells take place into the laser-injured site, however these cells gradually diminish over time. Apoptotic cell death may be involved, but the mechanism remains unclear.
To elucidate the role of apoptosis in CNV, we quantified CNV formation in wild type (WT) and apoptosis inducing factor (AIF) mutant mice (AIF-/Y). CNV was induced by laser photocoagulation with 532nm, 150mW, 100msec, 50µm settings. Eyes were enucleated at 1, 2, 4, and 12 weeks of age and were analyzed using immunohistochemistry, TUNEL, transmission electron microscopy (TEM), RT-PCR and western blotting. To test macrophage apoptosis, peritoneal macrophages induced by thioglycollate medium were collected from AIF-/Y and WT mice and cultured under starved conditions for 24 hours.
CNV size was increased in AIF-/Y mice compared to WT in 2, 4, 12 weeks after laser induction. Following laser injury, inflammatory / endothelial apoptosis detected by TUNEL was significantly lower in AIF deficient mice when compared to WT at 4 weeks. The AIF-/Y peritoneal macrophages showed less apoptosis compared to WT in culture under starved conditions.
Mice lacking AIF show substantial persistence of inflammatory / endothelial cells at the laser-injury site. Our data suggest that apoptosis plays an important role in laser-induced CNV, and therapeutic modulation of apoptosis via AIF may offer a new target for treatment of CNV.
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