Altered Ganglioside Expression Modulates the Pathogenic Mechanism of Thyroid Associated Ophthalmopathy by Increase in Hyaluronan

Abstract

Purpose: : To reveal the role of gangliosides in pathogenic mechanisms of Thyroid associated ophthalmopathy (TAO)

Methods: : We investigated the ganglioside profile in the orbital tissue of patients with TAO and examined the effect of exogenous gangliosides on the expression of hyaluronan and the morphology of orbital fibroblasts from subjects without inflammatory disease.

Results: : Trisialoganglioside 1b (GT1b) was significantly overexpressed in the orbital tissue of TAO patients compared to control tissue, while no significant difference was observed for either monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a). Moreover, mRNA levels of sialyltransferase I (SAT I) and SAT II were increased in TAO patients compared to control. GT1b-treated cells contained sparse flocculent precipitates in lysosomes due, at least in part, to an increase in hyaluronan. Correspondingly, the level of extracellular hyaluronan measured was increased in GT1b-treated orbital fibroblasts. The morphologic changes of orbital fibroblasts were induced by GT1b, but not by GM1 or GD1a. And these changes in GT1b-treated orbital fibroblasts were nicely attenuated by co-treatment with hyaluronidase.

Conclusions: : Our results suggest that gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of TAO by stimulating an increase in hyaluronan.

Keywords: orbit • autoimmune disease