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Ye Sun, Chi-Hsiu Liu, Yan Gong, Bertan Cakir, Steve Cho, Alexander Poblete, William Britton, James D Akula, Jing Chen, Lois E H Smith; A negative immune regulator SOCS3 controls laser-induced choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2989.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization (CNV) is the major cause of vision loss in neovascular age-related macular degeneration (AMD). Immune dysregulation has been linked with CNV clinically and experimentally, specifically, immune cells of myeloid origin are attracted to and control experimental CNV, but the underlying mechanisms are largely unknown. We identified a novel factor, suppressor of cytokine signaling 3 (SOCS3), that controls CNV through modulating inflammatory mediators, immune cell activation and infiltrationin myeloid cells.
We generated SOCS3 knock-out and knock-in mice using the Cre/loxP system. Myeloid specific Cre mice as well as mT/mG Cre reporter mice were used in laser-induced CNV mouse models of pathological NV. Real-time PCR, western blot and immunohistochemistry were used to analyze gene expression and protein localization. Confocal imaging, fundus fluorescein angiography and HE staining were used to identify phenotypes. FACS was used for immune cell population assay and immune cell isolation. NV was quantified using image J. Results are presented as mean ± SEM and were compared using the 2-tailed unpaired t-test. Statistical analyses were performed with GraphPad Prism (v6.0).
In the laser CNV mouse model, myeloid specific deletion of SOCS3 increased CNV by 30-40% (p<0.001, n=26-30), and myeloid specific overexpression of SOCS3 reduced CNV by ~25% (p<0.001, n=30). These data suggested that myeloid specific SOCS3 controls pathological NV in a laser-CNV model. Pharmacologic treatment with a SOCS3 activator suppressed CNV by 40% in the laser CNV model (p<0.001, n=45-50).
These findings suggested that overexpression of SOCS3 in myeloid cells suppressed CNV by controlling inflammatory mediators which control immune cell activation and infiltration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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