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Shaodan Zhang, Lin Du, Di Wu, WAI KIT CHU, Hailin Wang, Chi Liu; Antifibrotic effect of conbercept (KH902) on human tenon’s fibroblasts. Invest. Ophthalmol. Vis. Sci. 2018;59(9):476.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of conbercept (KH902) on the proliferation, migration, extracellular matrix production, and cytokine secretion of the human tenon’s fibroblasts (HTFs).
Human tenon’s tissue was obtained from adult strabismus patients during surgery. Primary cell culture for the HTFs was performed. Conbercept at 100ug/mL were administered for 24h in 10% serum conditions. The effect of conbercept on HTFs proliferation and cell viability was determined using MTT assay. Scratch wound assay was performed to evaluate the cell migration. The mRNA expressions of MKI67, alpha smooth muscle actin (a-SMA), fibronectin, collagen type I and caspase 3 were assessed by quantitative real-time PCR. Cell supernatants were tested for the concentrations of secreted VEGF, monocyte chemotactic protein (MCP)-1, fibroblast growth factor (FGF-b), tumor necrosis factor-a (TNF-a), interferon gamma (IFNγ), and platelet-derived growth factor-BB (PDGF-BB) using multiplex bead analysis.
Conbercept at 100ug/mL slightly reduced the cell viability in cultured HTFs (93.72% of control) and had no effect on the cell migration. MRNA expression of MKI67, a-SMA, fibronectin and collagen I was significantly downregulated by conbercept. The level of caspase 3 mRNA in conbercept treated HTFs had no difference with the controls. The concentrations of secreted VEGF (t=3.962,p=0.011）, FGF-b（t=4.735,p=0.005）, TNF-a(t=4.293,p=0.008) , and IFN-γ (t=2.796,p=0.038) were significantly lower in Conbercept treated cell supernatants compared with untreated controls.
Conbercept could effectively downregulate the fibrosis-related mRNA and protein expression in HTFs with no obvious effects on the cell proliferation and migration. It may be used as an independent or complementary anti-fibrotic agent to other antimetabolites in glaucoma filtering surgery.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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