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

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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.