Experimental Study of ZAPRINAST on Aqueous Outflow Mechanism

我们设计这项研究是为了找到一种方法来了解青光眼的治疗线索。我们发现，磷酸二酯酶5型特异性抑制剂zaprinast增加了去核牛眼的流出设施。由于该药增加cGMP，因此我们特别关注的是研究扎普利司特对眼内肌、流出设施和培养小梁网细胞形状的影响结果(1)构建了眼灌注系统。Zaprinast大幅增加了流出设施，增幅超过200%。另一方面，dB-cAMP仅在一定程度上改变了流出设施，分别为95.1±4.9,78.8±4.9,80.9±4.2%。(2) Zaprinast不诱导牛纤毛肌缩小或收缩。Zaprinast没有改变眼内肌的张力。然而，当肌预收缩时，0.1 ~ 100 μM的zaprinast使肌肉松弛。(3)扎普那司特和/或西地那非增加了牛眼的流出设施。Zaprinast比西地那非增加了更多的流出设施。(4)小梁网细胞和睫状肌的细胞培养研究：Zaprinast改变了小梁网细胞的细胞形态。扎普那司特在2小时内收缩细胞，西地那非在5小时内收缩细胞。我们进行了灌注研究，肌肉和细胞培养研究，以了解扎普利司特治疗青光眼的效果。Zaprinast可以增加眼的流出设施，而不收缩睫状肌，其效果比以往报道的要大得多，可能是未来青光眼的候选药物我们从最初的研究计划中改变的事项（费用）我们最初计划出国交流和介绍目前的研究。但不幸的是，消费供应不足，放弃了出国的计划。固定装置是按照最初的设计购买的。

We designed our study to find a method to understand a clue for curing glaucoma. We found that zaprinast, a specific inhibitor of phosphodiesterase type 5, increased the outflow facility of enucleated bovine eyes. Since the drug increases cGMP, it was a special concern for us to study the effect of zaprinast on intraocular muscles, outflow facility and shape of cultured trabecular meshwork cells.1 Results (1998-1999)(1) We structured eye-perfusion system.Zaprinast markedly increased the outflow facility by more than 200%. On the other hand, dB-cAMP changed the outflow facility only to some extent by 95.1±4.9, 78.8±4.9, 80.9±4.2%, respectively.(2) Zaprinast did not induce miosis or contraction of bovine ciliary muscle.Zaprinast did not alter the tone of the intraocular muscles. However, when the muscle was precontracted by carbachol, zaprinast (0.1 to 100 μM) relaxed the muscle.(3) Zaprinast and/or sildenafil increased the outflow facility of the bovine eye.Zaprinast had increased the outflow facility much more than sildenafil did.(4) Cell culture study of trabecular meshwork cells and ciliary muscles :Zaprinast altered the cell shape of trabecular meshwork cells. Zaprinast contracted the cell within 2 hours, and sildenafil in 5 hours.We performed the perfusion study, muscle- and cell cuture- studies to learn the effect of zaprinast to cure glaucoma.Zaprinast may be a candidate of glaucoma drug in future, because the drug could increase the outflow facility of the eye and did not contract the ciliary muscle, and the effect was much greater than ever reported.2 Matters which we changed from the initial research planning (fees)We initially planned to go abroad to communicate and make a presentation of the present study. Unfortunately, however, consumption supplies were insufficient and gave up the planned idea to go abroad. Fixtures were purchased as initially designed.