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D. Tang, S. Schaal, Q. Zeng, T. Tezel; Contribution of Adult Hematopoietic Stem Cells to Subretinal Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3354.
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To determine the contribution of adult hematopoietic stem cells (HSC) to subretinal choroidal neovascularization (SRNVM).
SRNVM was induced with a dfYAG (532 nm) laser in 10 C57BL/6J mice. 14 days after laser photocoagulation animals were perfused through heart under deep anesthesia with 2-million kDa-dextran-conjugated fluorescein and sacrificed. Enucleated globes were fixed in 4% paraformaldehyde and flat-mounts were stained with Cy3-conjugated anti-CD117 (C-kit receptor) antibody for the presence of HSC. The incidence of SRNVM and the number of C-kit positive spots were determined. The experiment was repeated with another group of 10 mice 3 days after receiving a total body irradiation of 900 rads. The incidence of SRNVM, the number of HSC-positive spots, and the morphometry of SRNVMs were compared bewteen the HSC-depleted animals and the control group.
C-kit + HSCs were identified in 72.7% of the control laser spots. In 92.3% of the spots they were a part of the neovascular complex. Irradiation decreased significantly HSC homing to laser spots (72.7% vs. 3.1%, p<0.001 at the laser spot) and to neovascular complex (92.3% vs. 20%, p<0.001). The incidence of SRNVM decreased in irradiated animals significantly (54.5% vs. 10.4%, p<0.001). Morphometric analysis revealed robust attenuation of the neovascular vessels with a decrease in the size of the neovascular complex in HSC-depleted animals (p<0.05).
Adult HSC contribute to the development of choroidal neovascularization. Pharmacological interference to HSC homing may provide a new therapeutic opportunity.
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