Steely H T, Browder S L, Julian M B, Miggans S T, Wilson K L, Clark A F
Department of Glaucoma Research, Alcon Laboratories, Fort Worth, Texas 76134.
Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2242-50.
Topical administration of glucocorticoids to the eye can lead to the development of ocular hypertension. This increase in intraocular pressure is caused by the heightened resistance to flow of aqueous humor from the eye, presumably at the trabecular meshwork (TM). This study reports the effects of dexamethasone (DEX) on the expression of the extracellular matrix protein fibronectin (FN) in cultured human TM cells (HTM). The expression of FN was evaluated in four HTM cell strains by epifluorescence microscopy and immunoblotting and autofluorography of electrophoretically separated cell proteins. There was a heterogeneous response of the four cell strains tested. Treatment of cell strain HTM4 with DEX (10(-7) mol/l) for 17 d caused an approximate doubling of cell-associated and secreted FN. This DEX-induced increase in FN expression was progressive after the first 7 d of treatment and was blocked partially with a glucocorticoid antagonist, cortexolone. By contrast, DEX treatment induced an intermediate 50-60% increase in FN expression in cell strains HTM10 and HTM2; in HTM6, FN was unchanged after exposure to the glucocorticoid. This model system may be useful to examine molecular changes associated with corticosteroid-induced ocular hypertension and evaluate glaucomatous changes in the TM because increased FN deposition occurs in the aqueous humor outflow pathway of patients with open-angle glaucoma.
眼部局部应用糖皮质激素可导致眼压升高。眼内压的这种升高是由于房水从眼内流出的阻力增加所致，推测是在小梁网（TM）处。本研究报告了地塞米松（DEX）对培养的人小梁网细胞（HTM）中细胞外基质蛋白纤连蛋白（FN）表达的影响。通过落射荧光显微镜、免疫印迹以及对电泳分离的细胞蛋白进行自发荧光成像，评估了四种HTM细胞株中FN的表达。所测试的四种细胞株呈现出异质性反应。用DEX（10⁻⁷mol/L）处理细胞株HTM4 17天，导致细胞相关和分泌的FN增加约一倍。DEX诱导的FN表达增加在处理的前7天后呈进行性，并且被糖皮质激素拮抗剂皮质酮部分阻断。相比之下，DEX处理在细胞株HTM10和HTM2中诱导FN表达增加50 - 60%；在HTM6中，暴露于糖皮质激素后FN无变化。该模型系统可能有助于研究与皮质类固醇诱导的眼压升高相关的分子变化，并评估小梁网中的青光眼性变化，因为在开角型青光眼患者的房水流出途径中会发生FN沉积增加。
