Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in rabbit and human vitreous

Abstract

Purpose: To investigate the effect of exogenous plasmin administration on the activity of endogenous matrix metalloproteinase-2 (MMP-2) in rabbit and human vitreous.

Design: Experimental animal study and interventional case series.

Methods: Human plasmin was injected into rabbit eyes. The active/pro-MMP-2 ratio in vitreous samples was calculated using the gelatin zymography. Scanning electron microscopy (SEM) was performed to observe the retinal surface. To evaluate the time course of MMP-2 activity, vitreous samples were collected after the injection of 0.5 IU of plasmin, and the active/pro-MMP-2 ratio was calculated in the same manner. Immunohistochemical analysis was performed to confirm the presence of MT1-MMP in the rabbit eye. Human vitreous samples obtained from vitreous surgeries were also used for similar studies.

Results: The active/pro-MMP-2 ratios in the vitreous after the injection of 0.25 IU or 0.5 IU of plasmin were significantly higher than that of the control (P < .05). SEM demonstrated that plasmin-treated eyes showed a smooth retinal surface that was dose-dependent. Time course evaluation of the active/pro-MMP-2 ratio in the vitreous after the administration of 0.5 IU of plasmin found a significant difference between the 5 and 15 minutes data points compared with that seen for the control. Immunohistochemical study revealed the presence of MT1-MMP in the inner retina. In human samples, the active/pro-MMP-2 ratio after the plasmin injection was significantly higher than the ratio observed before injection.

Conclusions: Our results suggested that activation of endogenous MMP-2 by exogenous plasmin is associated with the induction of posterior vitreous detachment.