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Abstract #6314 Published in IGR 3-2
Human Tenon's fibroblast-produced IFNβ and the prevention of T-cell apoptosis
Chang L; Crowston JG; Sabin CA; Khaw PTInvestigative Ophthalmology and Visual Science 2001; 42: 1531-1538
PURPOSE: Fibroblast-T-cell interactions may contribute to the development of chronic inflammation, a risk factor for trabeculectomy failure. This study was undertaken to determine whether and growth-arrested human Tenon's fibroblasts (HTF) can prevent cytokine deprivation-mediated T-cell apoptosis through the secretion of interferon (IFN)β. METHODS: HTF were used either untreated or pretreated with mitomycin-C (MMC; 0.1 or 0.5 mg/ml) or 5-fluorouracil (5FU; 25 or 50 mg/ml). IL2-deprived T cells were cocultured with HTF. T-cell viability was measured at specific time points. HTF-conditioned medium was used either untreated or treated with a neutralizing antibody against IFNβ to block its action, after which IL2-deprived T cells were added, and T-cell viability was measured. An image analysis system was used to determine the production of IFNβ by either untreated or MMC-treated HTF. RESULTS: T-cell viability was significantly greater when T cells were cocultured with both untreated and growth-arrested HTF than when T cells were cultured alone (day 7, p = 0.0001). Neutralizing the action of IFNβ blocked HTF-mediated T-cell rescue from apoptosis. Both untreated and growth-arrested HTF secrete IFNβ, and MMC at 0.4 mg/ml appeared to increase IFNβ production. CONCLUSIONS: Cytokine deprivation-mediated T-cell apoptosis can be prevented by the action of IFNβ secreted by both normal and growth-arrested HTF, which suggests that growth-arrested HTF can still participate in an aggressive wound-healing reaction by mediating a persistent inflammatory phase. This may partly explain why some trabeculectomies fail in high-risk patients, despite the use of antimetabolites.
Dr L. Chang, Wound Healing Research and Glaucoma Units, Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK. changevans@aol.com
Classification:
2.1 Conjunctiva (Part of: 2 Anatomical structures in glaucoma)
4 Tissue culture of ocular cells
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
