Intravenous Thrombolysis By Tissue-type Plasminogen Activator Deletion Mutant In A Rabbit Model Of Retinal Artery Occlusion

Objectives:1.To observe the nature course of experimental retinal artery occlusion established by photochemical method in a rabbit model and to validate the efficiency of the RAO model induced by this method in a certain period.2.To compare the efficiency and safety of intravenous thrombolysis by two kinds of tissue-type plasminogen activator deletion mutants in a rabbit model of retinal artery occlusion established by photochemical method.Methods:1.The nature course of the experimental retinal artery occlusion induced by photochemical method in a rabbit model10 pigmented rabbits were used in this study.The RAO was created in a random eye by a laser which central wavelength was 532nm following intravenous injection of rose bengal(5%solution,50mg/kg) through marginal ear vein.A laser was applied to a certain artery which has a distance from the accompanying vein at the optic disc margin.One hour later,the RAO was confirmed by fluorescein angiography(FFA).The animals were follow-up in the 1st,3rd,5th and 7th day by direct ophthalmoscope,fundus photography and FFA.All experimental eyes were enucleated under anaesthesia for histology examination.2.Intravenous thrombolysis by two kinds of tissue-type plasminogen activator deletion mutants in a rabbit model of retinal artery occlusion induced by the photochemical method.30 pigmented rabbits were used and randomly divided into 3 groups. experimental r-PA(0.9MU/kg),retavase(0.9MU/kg) and injectable water (10ml) was injected respectively through the marginal ear vein 1.5 hour later after the RAO model was created.4 hours and one day later,the RAO was observed by ophthalmoscope,fundus photography and FFA respectively while the blood was collected for PT,APTT,TT,Fbg,D-Dimer before drug administration and at lst,2nd,3rd,4th hour after that.all the experimental rabbits were examined by CT to exclude the intracranial hemorrhage.One day later after thrombolysis,All experimental eyes were enucleated under anaesthesia for histology examination.Results:1.The nature course of the experimental retinal artery occlusion induced by photochemical method in a rabbit model.At 1st and 3rd day the obstructed arteries didn't reopen in all experimental eyes.8 and 2 obstructed arteries reopened at 5th,7th day respectively.Histological examination showed that the vessel wall was integrated under the light microscope.2.Intravenous thrombolysis by two kinds of tissue-type plasminogen activator deletion mutants in a rabbit model of retinal artery occlusion induced by the photochemical method.reperfusion rate of experimental r-PA group,retavase group and control group was 70%,60%,0%respectively after drugs administration at 4th hour as same as at 1st day.Reperfusion rate of experimental r-PA group was not significantly different from retavase group's.TT,PT of retavase group increased significantly respectively from experimental r-PA group's.Fbg of retavase group decreased significantly respectively from experimental r-PA group's.There was no vitreous or retinal hemorrhage and no intracranial hemorrhage in all experimental rabbits. Histological examination showed that RAO was caused by intra-arterial thrombus and the vessel wall was integrated under the light microscope.Conclusion:There was no recanalization approved by FFA after 3 days in the rabbit model of retinal artery occlusion induced by photochemical method.It suggests that the RAO model can be used for thrombolysis study in 3 days. Two kinds of r-PA shows good thrombolytic effect and less tendency to hemorrhage complication,The thrombolytic effect has no significant difference between them.Compare to the retavase group,the experimental r-PA group shows less side-effect on the coagulation and fibrinolytic system.