Microscale Analysis of the Glycosaminoglycans of Human Trabecular Meshwork

Abstract

Glycosaminoglycans (GAGs) and proteoglycans of the trabecular meshwork may be involved in the pathogenesis of primary open angle glaucoma and of corticosteroid-induced glaucoma. Although numerous studies of GAGs have been performed on trabecular cells in monolayer culture and in animals, few studies have examined intact human meshwork. Using a new analytic method for quantitative determination of GAGs from individual meshworks, we studied the GAGs of human trabecular meshwork in normal eyes and intact meshwork from perfusion-cultured eyes. Eyes in the culture system were treated with dexamethasone for 21 days in an attempt to create a model of steroid glaucoma. The effect of ascorbate, also known to influence GAG levels, was examined in a preliminary study. Cultured trabecular meshwork had a significant decrease in total GAG levels when compared with meshwork from normal, noncultured eyes (1.16 +/- 0.54 ng/mug vs. 3.51 +/- 0.57 ng/mug; p < 0.01). Ascorbate tended to cause a decrease (28%) in the total level of GAGs, although the difference was not significant. No significant difference in mean GAG levels was found between the dexamethasone-treated and fellow control eyes. Dexamethasone was associated with a large biologic variability in total GAG level (coefficient of variation 89%). In an attempt to identify individual steroid responders mixed in with a group of nonresponders, analysis of individual eyes revealed three of nine eyes to have total GAGs 250% than fellow control eyes, although this variability could also be due to other causes. No consistent change in group mean intraocular pressures was found in the dexamethasone-treated eyes. Intraocular pressures were positively correlated with total GAG levels (r = 0.59; p < 0.01).