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Sang Jin Kim, Ji-Hyun Yun, Jung Hwa Ko, Hyun Ju Lee, Joo Youn Oh; Anti-inflammatory protein TSG-6 ameliorates laser-induced choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):6180.
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Inflammation plays a crucial role in the development of choroidal neovascularization (CNV). An anti-inflammatory protein, TSG (tumor necrosis factor-inducible gene)-6 has been shown to improve tissue repair by suppressing inflammation in eyes and other tissues. In this study, we investigated the effect of an intravitreal injection of recombinant TSG-6 in a rat model of laser-induced CNV.
CNV was induced by applying laser photocoagulation to the Bruch’s membrane in Brown Norway rats. Right after CNV induction, either recombinant TSG-6 (400ng) or the same volume of PBS was injected intravitreally. At days 1, 3, 7, and 14, retina and retinal pigment epithelium (RPE)-choroid-sclera were extracted and subjected to molecular and histological analyses. Also, on Day 3, retina and RPE-choroid tissues were subject to flow cytometric analysis.
Real-time RT-PCR showed that the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12a) and VEGFA were markedly increased in both retina and RPE-choroid-sclera by laser photocoagulation. The levels of cytokines reached peak at Day 1 and gradually decreased until day 14. TSG-6 injection significantly reduced the levels of pro-inflammatory cytokines and VEGFA in the retina and RPE-choroid-sclera at all examined time-points. Also, the area of CNV was significantly decreased in TSG-6-injected eyes, compared to PBS-injected controls. In choroid, laser treatment increased infiltration of CCR2+CD11b+CD11c+ or CCR2+CD11c+ cells, which were reduced by TSG-6 treatment.<br />
Intravitreal injection of TSG-6 resulted in the suppression of laser-induced CNV as well as the expression of pro-inflammatory cytokines and VEGF in rats. In addition, intravitreal TSG-6 reduced recruitment of migratory monocytes in choroid. These results suggest that TSG-6 may prevent the development of CNV in age-related macular degeneration or other diseases.
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