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

1. 降低眼压局部应用0.5%灰松酸酯（ga -酯）无明显的眼压降低反应。但是，在局部应用1% ga -酯后2小时观察到眼压（IOP）显著降低。局部应用2% ga -酯后，眼部降压反应持续5小时。局部应用浓度为0.5% ~ 2%的IOP后，家兔眼压呈剂量相关降低。cAMP在虹膜-睫状体ga -酯中的积累在100muM时显著提高了家兔虹膜-睫状体cAMP水平。ga -酯处理的虹膜-睫状体cAMP水平比IBMX处理的高4倍。2% ga -酯（50ul）局部应用1 ~ 24h后，睫状体形态无明显变化。无出血、间质水肿及炎性细胞侵袭。注2% ga -酯后，电子显微镜未见纤毛上皮形态学改变。用荧光光度法测得的GA治疗眼的平均水流速明显低于对照组。用异硫氰酸荧光素标记的右旋糖酐测量图上的流出量和巩膜流出量，局部应用Ga-酯并没有改变。5 .外用1 h后，结膜、角膜、房水、虹膜、睫状体的ga -酯的眼内渗透率分别为12.5%、0.065%、0.010%、0.017%和0.010%。噻莫洛尔对合成黑色素具有结合亲和力。而GA-酯不与合成黑色素结合。

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.