The effects of plasmin Kringle domains deficiency mutant on the interface of vitreous and retina in rabbit eyes

Background The vitreoretinal traction plays a critical role in the formation of macular hole and cystoid macular edema.Enzymatic vitreolysis has potential in relieving vitreoretinal traction as a simple and less invasive method in comparison with pars plane vitrectomy.ObjectiveThis study is to investigate the effects of plasmin mutant with kringle domains deficiency(Plm△K)on vitreoretinal interface in new Zealand white rabbits.Methods Plm△K was prepared through activating plasminogen mutant with Kringle domains deficiency (Plg△K) by tissue plasminogen activator (tPA).100μL of Plm△K at the dose of 0.5,1.0 and 1.5μmol/min was injected respectively into the vitreous of 48 New Zealand white rabbits and 16 eyes for each dose.B-scan and optical coherence tomography (OCT) were performed to detect the structure variety at the vitreoretinal interface in 1 day and 7 days after injection.The gross anatomy analysis with triamcinolone acetonide fine particle suspension,as well as histopathological examinations by scanning electron microscopy,was performed in the different time points mentioned above.Results Two peptide chains were determined with the relative molecular weight about 26000 and 5000 by the gel imaging analysis of reduced SDS-PAGE.Separation of the posterior vitreous cortex from retina was found after intravitreous injection under the B-scan and OCT.The ultrastructure change of vitreoretinal interface as well as the examination of fine particle suspension by triamcinolone acetonide demonstrated the same outcome.The degree of remnants of vitreous cortex showed the negative correlation with the dosage of Plm△K (r=-0.9516,P=0.048).No significant correlation was found between the degree of remnants of vitreous cortex and the action time(r=-0.720,P=0.470).There was no obvious morphological difference in outer layer of retina between control eyes and Plm△K-treated eyes.No drug-related adverse event was found after intravitreous injection of Plm△K.Conclusion Intravitreous injection of Plm△K alone can induce complete separation of vitreous from retina.This procedure is safe and effective. Key words: vitreoretinal interface; plasmin; Kringle domain; deficiency mutant