Studies in relation to endocrine exophthalmos: The biochemical composition of human retrobulbar connective tissue

Abstract

As part of studies on the pathogenesis of exophthalmos of Graves' disease, the biochemical composition of human retrobulbar tissue was investigated. The connective tissue was composed of 72.7% lipid, 23.8% water and 3.5% dried defatted tissue. Total tissue glycosaminoglycan (GAG) amounted to 0.18% of dried defatted tissue. Approximately 27% of the total hexosamine and 19% of the total tissue galactosamine were recovered in the GAG fraction. Cellulose microcolumn fractionation of GAG showed that the hyaluronic acid and dermatan sulfate were the two major GAG species.

In vitro synthesis of glycosaminoglycans in endocrine ophthalmopathy

“…In this sense, the question whether stimulation of retrobulbar fibro¬ blasts and increased release of GAG occur as conse¬ quences of primary immune reaction or as secondary phenomena remains unanswered (18). The potential singularity of retrobulbar fibroblasts in terms of ontogenetic development, physiology and HLA class II ex¬ pression having been realized (8,12), the effects of humoral as well as cellular immunity were to be assessed on retrobulbar fibroblasts in this study. While regulatory influence of distinct lymphokines on lung fibroblast GAG production has been reported (19), using retrobulbar fibroblasts, a significant binding of EO patients' IgG compared to controls' was shown (20) apart from a possibly modulatory function of IGF-I in the presence of IgG (21).…”

“…The activation of retrobulbar fibroblasts in EO orbits which express the HLA class II determinant (10) and the Pi blood group antigen (11) is mirrored in a stronger secretion of collagen and glycosaminoglycans (GAG), which are, with the exception of keratan sulfate, polysaccharides consisting of linear chains of repetitive disaccharide units comprising acetylic or sulfated hexosamines and hexuronic acids. The striking prevalence of hyaluronic acid and dermatan sulfate among the analysed GAG in normal retrobulbar tissue (12) has yet to be confirmed in affected EO tissue. The edematous swelling of extraocular muscles which themselves remain histologically intact (13) affects mainly the inferior and medial rectus muscles (8) and antedates, as the disease progresses, fibrosis, which is part of restrictive myopathy.…”