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理解治疗青光眼的线索。我们发现，扎普司特，一种特异性的磷酸二酯酶5型抑制剂，增加了牛眼去核后的流出能力。由于药物增加了cGMP，因此研究扎匹司特对眼内肌、小梁细胞流出能力和细胞形态的影响是我们特别关注的问题。1.结果(1998-1999)(1)我们构建了眼部灌流系统，扎匹司特使流出能力显著增加200%以上。而dB-cAMP仅在一定程度上改变流出功能，分别为95.1±4.9，78.8±4.9，80.9±4.2%。(2)扎匹司特不引起牛睫状肌收缩或收缩，不改变眼内肌的张力。然而，当肌肉被卡巴胆碱预收缩时，扎匹司特(0.1~100μM)对肌肉松弛。(3)扎匹司特和/或西地那非增加了牛眼的流出能力，扎匹司特增加流出能力的作用比西地那非更明显。(4)小梁细胞和睫状肌细胞培养研究：扎匹司特改变了小梁细胞的形态。扎匹司特在2小时内收缩细胞，西地那非在5小时内收缩细胞。我们进行了灌流研究、肌肉和细胞培养研究，以了解扎普司特治疗青光眼的效果。扎匹司特可能是未来青光眼药物的候选药物，因为该药物可以增加眼睛的流出能力，不收缩睫状肌，效果比以往报道的要大得多。2我们改变了最初的研究计划(费用)。我们最初计划出国交流和介绍本研究。然而，不幸的是，消费供应不足，放弃了出国的计划。按照最初的设计购买了固定装置。

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.