|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1999 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1998 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.