This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hansen, C. Articles by Kahaly, G. J. Search for Related Content PubMed PubMed Citation Articles by Hansen, C. Articles by Kahaly, G. J.

Increased Sulfatation of Orbital Glycosaminoglycans in Graves’ Ophthalmopathy¹

Department of Endocrinology/Metabolism, Gutenberg-University Hospital, Mainz, Germany

Address all correspondence and requests for reprints to: Prof. George J. Kahaly, University Hospital, Building 303, 55101 Mainz, Germany. E-mail: kahaly{at}endokrinologie.klinik.uni-mainz.de

Accumulation of interstitial glycosaminoglycans (GAG) in orbital tissue of patients with Graves’ ophthalmopathy (GO) leads to edema, increased orbital pressure, and proptosis. In this study, a new, highly sensitive, high performance liquid chromatography method was developed to determine the altered concentration and biochemical composition of different GAG polymers in orbital connective tissue of 27 GO patients and 18 controls. GAG were isolated by tissue homogenization and digestion, followed by sequential enzymatic GAG hydrolysis and high performance liquid chromatographic analysis of the resulting ,ß-unsaturated disaccharides. High recovery rates of 78 ± 6% (mean ± SE) and a detection limit of 4.0 µg/L (0.01 µmol/L) were obtained. Total tissue GAG amounted to 254 ± 16 µg/g wet tissue wt in patients and 150 ± 13 µg/g (P < 0.0001) in controls. Regarding the GAG polymers, marked differences were detected between patients and controls (chondroitin sulfate, 127 ± 13 vs. 47 ± 5 µg/g; hyaluronic acid, 56 ± 5 vs. 34 ± 4 µg/g; both P < 0.0001; dermatan sulfate, 77 ± 6 vs. 69 ± 6 µg/g; P < 0.05). In patients, chondroitin sulfate was the major GAG component (48 ± 6 vs. 31 ± 5% of total GAG in controls), whereas dermatan sulfate was dominant in controls (46 ± 8% vs. 30 ± 5%). The sulfated disaccharide digestion products were markedly increased (P < 0.0001) in patients, and the ratio of sulfated vs. total disaccharide content was 85 ± 6% vs. 65 ± 5% (P < 0.05) in patients and controls, respectively. As accumulation of negatively charged sulfate residues in GAG disaccharides results in enhanced water-binding capacity, beside inflammation and increased volume of the orbital adipose tissue, the altered structure and nature of sulfated GAG units in the orbit may be responsible for the pathogenic changes in Graves’ ophthalmopathy.

This article has been cited by other articles:

				G. J. Kahaly and W. H. Dillmann Thyroid Hormone Action in the Heart Endocr. Rev., August 1, 2005; 26(5): 704 - 728. [Abstract] [Full Text] [PDF]

				W. M. Wiersinga and M. F. Prummel Pathogenesis of Graves' Ophthalmopathy--Current Understanding J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 501 - 503. [Full Text]

				G. J. Kahaly, H.-P. Rösler, S. Pitz, and G. Hommel Low- Versus High-Dose Radiotherapy for Graves' Ophthalmopathy: A Randomized, Single Blind Trial J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 102 - 108. [Abstract] [Full Text]