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Effects of Dopamine Antagonists and Agonist on Cultured Human Tenon's Fibroblast Cells

Dopamine拮抗劑及同氣劑對培養人類之眼睛纖維母細胞生長之影響

摘要


根據過去的證據顯示,釀質使用抗青光眼眼藥可能會引起眼球Tenon’s纖維母細胞的增生,而影響日後青光眼手術的成功率。由於一些Dopamine拮抗劑及同形劑已被證實具有降眼壓的作用,未來有可能會吏用於臨床上當作抗青光眼的製劑。因此本研究是利用體外培養人類眼睛Tenon’s纖維母細胞的模式來探討這些藥對Tenon’s纖纖維母細胞的影響。其實驗結果顯示不同的Doamine拮抗劑:如domperi-done, haloperidol, moperone及loxapine均會抑制培養的人類眼球Tenon’s纖維母細胞3H-thymidine的攝取量,當藥品首先以0.5%溶解在dimethyl sulfoxide (DMSO)中,然後以細胞培養液由0.05%開始以10倍稀釋至0.00005時發現,domperidone抑制3H-thymidine的攝取則降到只有控制組的10.8%-72.4%,在halope-ridol降到28.6%-99.2%,在moperone降到9.8%-104.6%,loxapine則是降到控制組的938%-96.9%。而另一種dopamine同形劑:bromocriptine也能抑制人類眼球Tenon’s纖維母細胞3H-thymidine的攝取量,則降到控制組的25.1%(0.05%)到92.3%(0.00005%)。以上結果顯示上述的藥若在未來長期當作抗青光眼藥物時並不會刺激人類眼睛Tenon’s纖維母細胞的增生。

關鍵字

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並列摘要


It was found that long-term therapy with topical antiglaucoma drugs may increases the number of fibroblasts and inflammatory cells in the conjunctiva and Tenon’s capsule then decrease the success of glaucoma filtering surgery. Shnce somew dopamine antago-nists and agonists are reported to have ocular hypotensive effects, they could potentially be used as clinical antiglaucoma agents in future. In this study, several dopamine antagonists and agonists were evaluated in their effects on the fibroblast proliferation of ocular tissues with cultured human ocular Tenon’s fibroblast cels. It was found that do-pamine antagonists inhibited [3H]-thymidine uptake to 10.8%, 14.4%, 42.2% and 72.4% of control in domperidone, 28.6%, 67.7%,96.9% and 99.2% in haloperidol, 9.8%, 18.9%, 103.5% and 104.6% in moperone and 9.8%, 24.7%, 70.8% and 96.9% in loxa-pine respectively, while the 0.5% concentration of drugs were dissolved in dimethyl sul-poxide (DMSO) followed by dilution in culture medium to final concentrations ranging from 0.05%, 0.005%, 0.0005% to 0.00005%. In the case of dopamine agonist, bromo-criptine, the proliferation of cultured human Tenon’s fibroblast cells was also inhibited for 25.1% of the control at 0.05% concentration and 92.3% of the control at 0.00005% concentration. These results indicate that these dopamine drugs have a potential long-term application in the treatment of glaucoma without having the stimulating effect on the proliferation of human Tenon’s fibroblast cells.

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