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


METHODS
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.
Takano
Akiomi
A
Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Honjo, Kumamoto, Japan.
Hirata
Akira
A
Inomata
Yasuya
Y
Kawaji
Takahiro
T
Nakagawa
Kuniko
K
Nagata
Shirou
S
Tanihara
Hidenobu
H
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D005341:Fibrinolysin / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D011817:Rabbits; D012160:Retina / Q000201:enzymology; D014821:Vitrectomy; D014822:Vitreous Body / Q000187:drug effects* / Q000201:enzymology*
D005343:Fibrinolytic Agents; D005341:Fibrinolysin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2