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N. Sugi, S. Aoki, S. Mukai, N. Ibaraki; Oxygen-Induced Retinopathy Increases Glial Scarring and Microglial Expression of TNF-Î± in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6111. doi: https://doi.org/.
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Oxygen-induced retinopathy (OIR), a mouse model of retinopathy of prematurity, is characterized by retinal ischemia with retinal neovascularization (NV) and inflammation. TNF-alpha is a pro-inflammatory cytokine that activates microglia and glial cells. We hypothesize that inflammation in OIR causes activation of microglia, release of TNF-alpha, and glial scarring.
P7 mice (C57BL/6) received 75% O2 for 5 days followed by room air. Control mice were kept at room air. Mice were sacrificed at P12, P17, and P31. Fluorescein-dextran was perfused to visualize the retinal vessels. The retina was evaluated at by histology (H&E) and by immunohistochemistry (IHC) for Muller cells (anti-GFAP), microglia (anti-Iba1), and TNF-alpha (polyclonal anti-TNF-alpha for IHC co-stained with anti-microglia).
OIR mice at P12 and P17 displayed areas of non-perfusion and NV in the midperipheral retina. At P31 these was significant reperfusion of the retinal vessels and absence of NV. P17 and P31 mice exhibited retinal damage with thinning of the inner nuclear layer (INL). P17 mice displayed glial scarring of astrocytes in the non-perfused retina and increased GFAP expression consistent with Muller cell activation. These findings persisted at P31 but were not present at P12. At P 17 and P31, the number of microglia was increased in the ganglion cell layer and the inner plexiform layer. Activated microglia co-localized with TNF-alpha expression at P17.
OIR mice showed activation of microglia and Muller cells and retinal damage in the INL with glial scarring that appeared by P17 and persisted after remodeling of retinal vasculature. Inflammation appeared to be in part from hyperoxia-induced activation and migration of microglia and release of TNF-alpha.
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