Experimental Study on Changes of Intraocular Pressure by the Application of Griseolic Acid

应用灰油酸改变眼压的实验研究

• 批准号: 63570832
• 负责人: MISHIMA Hiromu
• 金额: $ 1.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570832/
• 关键词: griseolic acid; cAMP-phosphodiesterase inhibitor; intraocular pressure; cyclic AMP; Morphological change; aqueous humor dynamics; ocular penetration; melanin; cAMP分解酵素阻害剤; 房水循環動態; CAMP-poshodi esterase阻害剤; 眼圧下降; griseolic acid; 緑内障

1. REDUCTION IN INTRAOCULAR PRESSURE Topical application of 0.5% griseolic acid-ester (GA-ester) showed no significant ocular hypotensive response. But, a significant reduction in intraocular pressure (IOP) was observed at 2hr after topical application of 1% GA-ester. The ocular hypotensive response lasted 5 hrs after topical application of 2% GA-ester. IOP in rabbits was reduced in a dose-related manner following topical application of concentration of 0.5% to 2%.2. cAMP ACCUMULATION IN IRIS-CILIARY BODY GA-ester at 100muM markedly increased the cAMP levels in rabbit iris-ciliary bodies. cAMP levels in GA-ester treated iris-ciliary body is four times higher than in IBMX treated one.3. MORPHOLOGICAL CHANGES IN IRIS-CILIARY BODY Topical application of 2% GA-ester (50ul) caused nb morphological changes in ciliary process at 1 to 24h. No bemorrhage, no stromal edema nor invasion of inflammatory cells were observed. Even electron micrograph could not detect any morphological changes in the ciliary epithelium after instillation of 2% GA-ester.4. CHANGES IN AQUEOUS HUMOR DYNAMICS The mean aqueous flow rate measured by fluorophotometry was significantly lower in GA- treated eyes than in control eyes. Topical application of Ga- ester did not alter tonographic outflow or uveoscleral outflow measured using fluorescein isothiocyanate labeled-dextran.5. INTRAOCULAR PENETRATION OF GRISEOLIC ACID-ESTER 1 hour after topical application, 12.5%, 0.065%, O.010%, 0.017% and 0.010% of topically applied GA-ester was detected, respectively, in the conjunctive, cornes, aqueous humor, iris and ciliary body.6. AFFINITY OF GRISEOLIC ACID -ESTER FOR SYNTHETIC MELANIN Timolol exhibited binding affinity to synthetic melanin. But, GA- ester did not bind to synthetic melanin.

1.眼内压的降低局部应用0.5%灰胆酸酯（GA-酯）没有显示出显著的眼部肿胀反应。但是，在局部应用1%GA-酯后2小时观察到眼内压（IOP）显著降低。局部应用2%GA-酯后，眼部肿胀反应持续5小时。局部应用0.5%至2%的浓度后，兔眼内压以剂量相关的方式降低。cAMP在虹膜睫状体中的积聚GA-酯在100 μ M时显著增加兔虹膜睫状体中的cAMP水平。GA-酯处理的虹膜睫状体中的cAMP水平比IBMX处理的高四倍。虹膜睫状体的形态学变化2%赤霉素酯（50 μ l）局部应用1 ~ 24小时引起睫状体形态学变化。未见出血、间质水肿及炎性细胞浸润。即使电镜下也未观察到2%赤霉素酯滴眼后睫状体上皮的形态学变化。房水流量的变化通过荧光光度法测量的平均房水流量在GA处理的眼睛中显著低于对照眼睛。局部应用镓酯并不改变张力描记术或用异硫氰酸荧光素标记的葡聚糖测量的葡萄膜巩膜流出量。赤霉酸酯的眼内渗透性局部应用后1小时，在结膜、角膜、房水、虹膜和睫状体中分别检测到12.5%、0.065%、0.010%、0.017%和0.010%的局部应用赤霉酸酯。噻吗洛尔对人工合成黑色素具有亲和力.但是，GA-酯不与合成黑色素结合。

项目成果

Mishima, H.: "Ocular pharmachology of anti-glaucomatous drugs: New drugs effecting on intracellular mediator." J.Eye :1990.

Mishima, H.：“抗青光眼药物的眼部药理学：影响细胞内介质的新药。”

Mishima, H.: "A cyclic AMP phosphodiesterase inhibitor, a derivatives of griseolic acid, lowers Rabbit intraocular pressure." Curr. Eye Res.:1990.

Mishima, H.：“一种环 AMP 磷酸二酯酶抑制剂，一种灰油酸衍生物，可降低兔眼压。”

Hiromu Mishima: "Effect griseolic acid cAMP-phosphodiesterase inhibitory on aqueous humor dynamics in rabbits" Current Eye Research.

Hiromu Mishima：“灰酚酸 cAMP-磷酸二酯酶抑制对兔子房水动力学的影响”当前眼科研究。

三嶋弘: "グリセオ-ル酸とメラニン色素" あたらしい眼科.

三岛浩：“灰油酸和黑色素”新眼科。

Mishma,H.K;kiuchi,Y.,et al: Current Eye Res.

Mishma，H.K；kiuchi，Y.，等人：当前眼科研究。