Enzymatic vitreolysis with recombinant microplasminogen and tissue plasminogen activator

Abstract

Purpose: To generate microplasmin (μPlm) using recombinant microplasminogen (μPlg) and recombinant tissue plasminogen activator (rt-PA) before intravitreous injection and to investigate the efficacy of μPlm in inducing posterior vitreous detachment (PVD). Methods: Forty-eight female or male New Zealand white rabbits were randomized into three groups. Recombinant human μPlg was incubated with rt-PA with a 200:1molar ratio at 37°C for 40min. The right eyes of groups 1, 2, and 3, were injected with 0.5, 1.0, and 1.5U μPlm in 0.1ml respectively, and 0.1ml balanced salt solution (BSS) was injected into the left eye as controls. Scanning electron microscopy (SEM), gross specimen examination, B-ultrasonography and optical coherence tomography (OCT) were performed to detect vitreoretinal interface. Results: Over eighty percent of recombinant human μPlg could be activated to active μPlm by rt-PA after 40min incubation. Complete PVD was found at vitreous posterior pole of μPlm-treated eyes without morphological change of retina. Complete PVD of 25, 75, and 87.5% rabbit eyes was induced by 0.5, 1.0 and 1.5U recombinant μPlm respectively on day 1. The remnants of vitreous cortex at the posterior pole were dependent on the concentration of μPlm. Among the four approaches for detecting PVD, SEM, gross specimen examination, and B-ultrasonography were more effective methods than OCT. Conclusion: Intravitreous injection of 1.5U μPlm can effectively induce complete PVD in rabbit eyes on day 1 without morphological change of retina.