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Marcus James Hooper, John D Ash; In the LPS-induced uveitis model, gp130 activation in retinal neurons and Müller glia dampens neutrophil infiltration to prevent excessive inflammation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5743.
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Leukemia inhibitory factor (LIF) is an IL-6 family cytokine, which has been shown by our lab to be neuroprotective in both induced and inherited models of retinal degeneration. LIF signals through the gp130 receptor, which is expressed by both retinal cells and bone marrow-derived cells. The purpose of this study was to determine whether this potent neuroprotective pathway also protects the neural retina from an excessive inflammatory response. This will test our hypothesis that gp130 signaling in the retina plays a role in protecting from excessive inflammation.
Inflammation was induced by intravitreal LPS injection in chx10-cre;gp130f/f, and tie2-cre;gp130f/f mice. These mice will have a retinal-specific or vascular and myeloid-specific knockout of gp130, respectively. Cre-negative mice were also injected as wild-type control mice. Retinal inflammation was examined by spectral domain optical coherence tomography (SD-OCT). Quantification of infiltrating cells was determined three days following injection by flow cytometry and histology.
OCT analysis demonstrated that LPS-induced cellular infiltration in all mice. However, mice with retina-specific knockout of gp130 had dramatically increased infiltration in the vitreous compared with LPS-injected wild type mice (cre-). Using flow cytometry, we determine that there were more total CD45+ cells in retina-specific knockout mice. Most of the increase in CD45+ cells can be accounted for by an increase in GR1+ neutrophils. These cells were 67.1% of the CD11b+ compartment in LPS-injected retina-specific knockout mice, but only 48.8% and 31.9% in wild type and myeloid-specific knockout mice respectively.
Our data show that gp130 signaling in retinal cells reduces neutrophil infiltration. These data suggest that activation of gp130 can function to protect the retina from tissue damage cause by excessive neutrophil infiltration.
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