Fig. 3.

Overview of the mechanisms involved in the action of oxidative stress in the pathogenesis of GO. The mechanisms that lead to the development of GO are triggered by the activation of helper T cells recognizing thyrotropin hormone receptor (TSHR) peptides presented by CD34+/CD40+ OF and the binding of TSHR on these cells by TRAb. These interactions induce the secretion of inflammatory cytokines, chemokines, and ROS and enhanced HA production and adipogenesis in OF. The resulting connective tissue remodeling causes various degrees of extraocular muscle enlargement and orbital fat expansion. Oxidative stress may exert a dual action in GO, acting in immunocompetent cells as well as in OF and adipocytes, thereby worsening the autoimmune response and promoting fibroblast proliferation and differentiation into adipocytes, as well as the release of HA and inflammatory cytokines. TNF-α, tumor necrosis factor-α; RANTES, regulated on activation, normal T cell expressed and secreted.