Altered ganglioside expression modulates the pathogenic mechanism of thyroid-associated ophthalmopathy by increase in hyaluronic acid.
OBJECTIVE
The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO).


METHODS
The gangliosides profile and mRNA level of sialyltransferases of the orbital tissues from TAO patients (n = 5) and non-TAO subjects (n = 4) were investigated. In addition, the effect of exogenous gangliosides on the expression of hyaluronic acid was examined in orbital fibroblasts. For in vitro experiments, we used four different strains of cells obtained from non-TAO subjects with at least three replicates for each strain.


RESULTS
Trisialoganglioside 1b (GT1b) was significantly overexpressed in the orbital tissue of TAO patients compared with control tissue, whereas no significant difference was observed for either monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a) by digital analyses of immunohistochemical images. Moreover, mRNA levels of sialyltransferase (SAT)-I and SAT II were increased in TAO patients compared with control. Exogenous GT1b strongly induced the morphologic changes related to an accumulation of sparse flocculent precipitates in lysosomes and increased the extracellular hyaluronic acid level in orbital fibroblasts with the induction of hyaluronic acid synthase, which were less by GD1a but not by GM1. The GT1b-induced morphologic changes of cells were due, at least in part, to an increase of intracellular hyaluronic acid. Co-treatment of hyaluronidase nicely attenuated the morphologic changes in orbital fibroblasts. Thy-1(+) orbital fibroblasts were more capable of producing hyaluronic acid by exogenous GT1b.


CONCLUSIONS
The results suggest that gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of TAO by stimulating an increase in hyaluronic acid.
Kook
Koung Hoon
KH
Department of Ophthalmology, Ajou University School of Medicine,Yeongtong-gu, Suwon 443-721, Korea. drkook@ajou.ac.kr
Choi
Youn-Hee
YH
Kim
Yu Rim
YR
Park
Soo Jung
SJ
Jou
Ilo
I
Kim
Sung Joo
SJ
Lee
Sang Yeul
SY
D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005677:G(M1) Ganglioside / Q000502:physiology; D005732:Gangliosides / Q000502:physiology*; D049970:Graves Ophthalmopathy / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000235:genetics; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D015703:Antigens, CD; D005677:G(M1) Ganglioside; D005732:Gangliosides; D006820:Hyaluronic Acid; D012333:RNA, Messenger; D012799:Sialyltransferases; C025447:sialogangliosides; C016481:trisialoganglioside GT1; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase