Chang, Lydia Pei-Yu; (2002) Fibroblast Interferon-beta mediated Prevention of T Cell Apoptosis; its Relationship with the development of Excessive Conjunctival Scarring. Doctoral thesis (M.D.), UCL (University College London).

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Abstract

Scarring plays a major role in ocular morbidity including the failure of glaucoma filtration surgery due to aggressive conjunctival scarring. Chronic inflammation and age are clinical risk factors for the failure of glaucoma filtration surgery due to an excessive wound healing response. Antimetabolites such as 5-fluorouracil and mitomycin-C are employed to reduce wound healing and improve the surgical success rate. The amount of scar tissue formation may be partly governed by the level of activity of inflammatory cells and fibroblasts during the wound healing reaction as well as the duration of their action. There is considerable evidence to suggest that inflammatory cell and fibroblast interactions play an important role in excessive scar tissue formation. One such interaction may be fibroblast- mediated prevention of T cell apoptosis, which has been shown to contribute to the development of chronic inflammatory conditions such as eczema and rheumatoid arthritis. This thesis provides evidence showing that human Tenon's fibroblasts rescue cytokine-deprived T cells from apoptosis through the production of Interferon-beta. Furthermore, both old and young fibroblasts can mediate this rescue, however young fibroblasts appear to be able to do it more for a short period of time. Antimetabolite-treated Tenon's fibroblasts are also able to prevent T cell apoptosis. We demonstrate the in vitro and in vivo production of Interferon-beta by Tenon's fibroblasts, showing that its production may be increased by treatment of fibroblasts with mitomycin-C and transforming growth factor-beta. This thesis indicates an important T cell/fibroblast interaction, which could play a crucial role in the development of chronic inflammation and persistent conjunctival scarring.

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