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N. Sugi, S. Aoki, N. Ibaraki; TNF-Alpha Increases Perfusion but Triggers Retinal Damage in Oxygen Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):372.
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Our previous results indicated that oxygen induced retinopathy (OIR) coincided with retinal damage, inflammation, and activation of microglia that expressed TNF-alpha. It is unclear whether hyperoxia-triggered inflammation is either destructive, or an essential part of healing injured tissue. We hypothesize it is possible to reduce OIR by inhibiting the destructive components of inflammation and/or increasing the wound healing components. In these experiments we examined the function of TNF-alpha in OIR.
OIR was induced in postnatal C57BL/6 mice by delivering 75% oxygen for 5 days (from P7 to P12) followed by room air. Five days later (P17) mice received an intravitreal injection of 10ng of mouse recombinant-TNF-alpha into the left eye. As a negative control, mice received an intravitreal injection of saline. Retinas were examined for: (i) areas of non-perfusion in retinal vasculature, (ii) activation of glia and microglia (via GFAP and Iba1 expression), (iii) expression of vascular endothelial growth factor receptor 2 (VEGF-R2), and (iv) retinal damage (via H&E staining).
In order to determine the function of TNF-alpha in OIR, mice received either exogenous TNF-alpha treatment, or saline (negative control). On day P24 after mice received TNF-alpha there was a significant increase in retinal perfusion as compared with the negative control. Increased perfusion coincided with an increased expression of VEGF-R2. However, TNF-alpha treatment also coincided with activation of Muller cells and microglia that mediated increased retinal folding and thinning of the inner nuclear layer.
Increased TNF-alpha following hyperoxia significantly increased expression of VEGF-R2 that accelerated re-perfusion of retinal vessels. However, TNF-alpha also activated glia that triggered increased retinal damage. These data imply that TNF-alpha triggered re-perfusion may be beneficial in OIR, if activation of glia can be blocked.
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