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D. S. Dace, A. A. Khan, R. S. Apte; Interleukin-10 Regulates Pathological Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2526.
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Our laboratory has reported that interleukin-10 (IL-10) deficient mice demonstrate reduced choroidal neovascularization (CNV) compared to wild-type mice in a laser-injury model of CNV. This new study attempts to determine whether IL-10 deficiency influences retinal angiogenesis in a model of hypoxia-induced retinal neovascularization.
P7 IL-10-/- and wild-type mice were exposed to 75% O2 for 5 days, followed by 5 days of normal O2 levels. Angiogenesis was evaluated using flat-mounts of fluorescein-perfused retinas and histology. Retinal inflammatory macrophages were characterized by fluorescent microscopy of perfused retinas. Gene expression of retinal macrophages was performed using quantitative real-time RT-PCR. Wild-type mice were treated with blocking antibodies to IL-10. The inhibition of vascular endothelial cell proliferation was assessed by treatment of wild-type and IL-10-/- macrophages with normoxic or hypoxic conditions.
Retinal neovascularization was decreased in IL-10-/- mice compared to wild-type control mice, as determined by fluorescent angiograms of retinal flatmounts and histology of whole globes. Ischemia resulted in a significant infiltrate of F4/80+ cells into the retina of both wild-type and IL-10-/- mice. Nitric oxide, a potential pro-angiogenic molecule in the retina, was highly upregulated in wild-type retinal macrophages but not in IL-10-/- retinal macrophages. Treatment of pups with blocking antibodies to IL-10 resulted in significantly less retinal angiogenesis compared to isotype control treated mice. IL-10-/- macrophages that were exposed to hypoxic conditions significantly inhibited the proliferation of vascular endothelial cells in vitro, whereas hypoxic wild-type macrophages did not.
IL-10 regulates retinal neovascularization, and may be an attractive therapeutic target in order to suppress the development of blood vessels in response to retinopathy of prematurity (ROP) or diabetic retinopathy.
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