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Enzymatic vitreolysis with recombinant microplasminogen and tissue plasminogen activator
1Department of Molecular Genetics, Shanghai Medical School and Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, Shanghai, PR China.
Purpose:
To generate microplasmin (microPlm) using recombinant microplasminogen (microPlg) and recombinant tissue plasminogen activator (rt-PA) before intravitreous injection and to investigate the efficacy of microPlm in inducing posterior vitreous detachment (PVD).
Methods:
Forty-eight female or male New Zealand white rabbits were randomized into three groups. Recombinant human microPlg was incubated with rt-PA with a 200:1 molar ratio at 37 degrees C for 40 min. The right eyes of groups 1, 2, and 3, were injected with 0.5, 1.0, and 1.5 U microPlm in 0.1 ml respectively, and 0.1 ml 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 microPlg could be activated to active microPlm by rt-PA after 40 min incubation. Complete PVD was found at vitreous posterior pole of microPlm-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 1.5 U recombinant microPlm respectively on day 1. The remnants of vitreous cortex at the posterior pole were dependent on the concentration of microPlm. Among the four approaches for detecting PVD, SEM, gross specimen examination, and B-ultrasonography were more effective methods than OCT.
Conclusion:
Intravitreous injection of 1.5 U microPlm can effectively induce complete PVD in rabbit eyes on day 1 without morphological change of retina.
Insights
Recombinant microplasmin (microPlm) effectively induces posterior vitreous detachment (PVD) in rabbit eyes. Intravitreous injection of 1.5 U microPlm achieved complete PVD on day 1 without retinal damage.
Area of Science:
- Ophthalmology
- Biochemistry
- Regenerative Medicine
Background:
- Posterior vitreous detachment (PVD) is a common cause of visual impairment.
- Current treatments for PVD are limited.
- Recombinant microplasmin (microPlm) offers a potential therapeutic agent for PVD.
Purpose of the Study:
- To generate microplasmin (microPlm) from recombinant microplasminogen (microPlg) using recombinant tissue plasminogen activator (rt-PA).
- To evaluate the efficacy of intravitreous microPlm injection in inducing PVD in a rabbit model.
- To assess the safety of microPlm by examining retinal morphology.
Main Methods:
- Recombinant human microPlg was activated to microPlm using rt-PA.
- Different concentrations of microPlm (0.5, 1.0, 1.5 U) were injected intravitreously into rabbit eyes.
- Control eyes received balanced salt solution (BSS).
- Vitreoretinal interface changes were assessed using SEM, gross examination, B-ultrasonography, and OCT.
Main Results:
- Over 80% of microPlg was activated to microPlm within 40 minutes.
- Intravitreous microPlm induced PVD in a dose-dependent manner.
- Complete PVD was observed in 87.5% of eyes treated with 1.5 U microPlm on day 1.
- No morphological changes in the retina were detected.
- SEM, gross examination, and B-ultrasonography were superior to OCT for PVD detection.
Conclusions:
- Intravitreous injection of 1.5 U microPlm is an effective method for inducing complete PVD in rabbit eyes.
- MicroPlm demonstrates a favorable safety profile, with no observed retinal toxicity.
- This study supports the potential of microPlm as a therapeutic agent for PVD.
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