Williams D E, Nguyen K D, Shapourifar-Tehrani S, Kitada S, Lee D A
Jules Stein Eye Institute, UCLA School of Medicine 90024-7004.
Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2233-41.
Evidence has been found suggesting that long-term therapy with topical antiglaucoma medications may decrease the success of glaucoma filtering surgery. To investigate this question further, the antiproliferative effects of the preservative benzalkonium chloride and three pure and commercially available beta-adrenergic antagonist preparations (timolol, betaxolol, and levobunolol) were studied on tissue cultures of human Tenon's capsule fibroblasts. Each drug preparation was tested on three different cell lines. Fibroblast growth was measured with tritiated thymidine uptake and hexosaminidase assays. Trypan blue uptake was used to assess cell viability microscopically. The commercially available preparations containing benzalkonium chloride and those of betaxolol and levobunolol without the preservative had similar inhibitory doses for 50% of cells. The timolol preparation without preservative was significantly less toxic than its commercially available one. The three tested beta-adrenergic blockers did not stimulate fibroblast proliferation directly in this in vitro model. Even when the cultures were washed free of the drugs, growth continued to be suppressed, suggesting that the inhibition was not reversible. An increase in fibroblasts and inflammatory cells after long-term antiglaucoma medical therapy thus may be caused not by a direct stimulation of cell proliferation but by chronic inflammation from the irritating effects of antiglaucoma medications and/or their preservatives.
已有证据表明，长期使用局部抗青光眼药物治疗可能会降低青光眼滤过手术的成功率。为了进一步研究这个问题，研究了防腐剂苯扎氯铵以及三种纯的市售β-肾上腺素能拮抗剂制剂（噻吗洛尔、倍他洛尔和左布诺洛尔）对人Tenon囊成纤维细胞组织培养物的抗增殖作用。每种药物制剂在三种不同的细胞系上进行测试。通过氚标记胸腺嘧啶核苷摄取和己糖胺酶测定来测量成纤维细胞生长。台盼蓝摄取用于显微镜下评估细胞活力。含有苯扎氯铵的市售制剂以及不含防腐剂的倍他洛尔和左布诺洛尔制剂对50%的细胞具有相似的抑制剂量。不含防腐剂的噻吗洛尔制剂的毒性明显低于其市售制剂。在这个体外模型中，三种测试的β-肾上腺素能阻滞剂没有直接刺激成纤维细胞增殖。即使将培养物中的药物冲洗掉，生长仍持续受到抑制，这表明这种抑制是不可逆的。因此，长期抗青光眼药物治疗后成纤维细胞和炎性细胞的增加可能不是由细胞增殖的直接刺激引起的，而是由抗青光眼药物和/或其防腐剂的刺激作用导致的慢性炎症引起的。
