Exogenous glycosaminoglycans stimulate hyaluronic acid synthesis by cultured human trabecular-meshwork cells

Addition of hyaluronic acid (50-200 micrograms ml-1) to the defined, serum-free media of cultured human trabecular-meshwork cells resulted in an increase of glycosaminoglycan (GAG) synthesis as measured by the incorporation of [14C]glucosamine. Lesser stimulatory effects were exerted by dermatan sulfate and chondroitin-4- or -6-sulfate. Nearly 90% of the labeled GAGs were found to be exerted into the medium and ea. 10% were associated with the cell layer. Mainly hyaluronic acid synthesis was stimulated by the exogenous GAGs. Analysis of the GAG-pattern revealed that exogenous hyaluronic acid stimulated hyaluronic acid synthesis (positive feedback), while exogenous dermatan sulfate and chondroitin sulfate had additional effects on chondroitin sulfate synthesis. Cell growth of these cultures, which exhibited a limited proliferative capacity (ca. 18 population doublings during their life span) was not affected by the GAG treatment. Thus, exogenous hyaluronic acid and to a lower degree dermatan sulfate or chondroitin sulfate appeared to interfere with the GAG-metabolism of these human trabecular-meshwork cells in culture.