Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro.
Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro.
复制标题
地塞米松治疗可减少体外灵长类小梁网细胞透明质酸的形成。
作者：
S. Engelbrecht;A. Siegner;P. Prehm;E. Lütjen
目前尚不清楚施累姆氏管筛状层中存在的透明质酸（HA）的功能意义。它可能有助于实际的流出阻力，但相对惰性的分子也可能是必要的，以防止较大的分子粘附到筛状网络。因此，HA可能会阻止流出阻力的增加。众所周知，在许多患者中用地塞米松（DM）治疗导致眼内压升高，推测是由于流出阻力增加。为了阐明HA形成的不平衡是否可能参与这些变化，我们用500 nM DM处理人小梁细胞以及对照细胞系（睫状肌细胞、巩膜成纤维细胞）的汇合培养物24小时或12天，并使用0.05 mM D-[6- 3 H]氨基葡萄糖盐酸盐掺入试验测量HA合成。在所有六个细胞系的研究有一个显着减少HA合成后，短期和长期的治疗与DM相比，未经处理的控制。小梁细胞对DM治疗的这种反应不同于报道的DM对细胞外基质的许多其他组分如纤连蛋白和弹性蛋白的合成的影响，这些组分在DM治疗后增加。如果在细胞培养物中观察到的DM效应在体内起作用，则HA形成减少可能导致流出途径功能受损。
The functional significance of Hyaluronan (HA) present in the cribriform layer of Schlemm's canal is not known. It may contribute to the actual outflow resistance but the relatively inert molecule might also be necessary to prevent adherence of larger molecules to the cribriform network. Thus HA might rather prevent an increase in outflow resistance. It is well known that treatment with Dexamethasone (DM) in a number of patients leads to an increase in intraocular pressure presumably due to an increase in outflow resistance. To clarify whether an imbalance in HA formation might be involved in these changes we have treated confluent cultures of human trabecular cells as well as control cell lines (ciliary muscle cells, scleral fibroblasts) with 500 nM DM for 24 hr or 12 days and have measured HA-synthesis using incorporation assays with 0.05 m D-[6-3H] Glucosamine hydrochloride. In all six cell lines investigated there was a significant decrease in HA-synthesis following short and long term treatment with DM when compared with the untreated controls. This reaction of trabecular cells to DM treatment is different from the DM effect reported on the synthesis of many other components of the extracellular matrix like fibronectin and elastin which increase after DM treatment. If the DM-effect seen in cell cultures plays a role in vivo decreased formation in HA could result in impaired function of the outflow pathways.