MMP-9 inhibition facilitates amacrine cell loss after ouabain-induced retinal damage.
Retinal ischemia is a common risk factor for visual impairment and blindness. Two common changes after retinal ischemia are retinal ganglion cell (RGC) loss and Müller glial cell (MGC)-mediated endogenous repair. Matrix metalloproteinase 9 (MMP-9) has been shown to be responsible to RGC death. However, the effects of MMP-9 on the loss of other neurons and the reactivity of MGCs after retinal injury remain unclear. Ouabain, a Na/K-ATPase inhibitor, was injected into the vitreous body of rat eyes to induce cell death in the inner nuclear layer (INL). MMP-9 expression and activation in the retinas were examined by gelatin zymography and immunohistochemistry. The role of MMP-9 inhibitor (MMP-9i) in ouabain-treated retinas was assessed. After ouabain injection, there was an upregulation of MMP-9 activity in the inner retinas, and the activation of MMP-9 reached a maximum at 2 day. Unexpectedly, MMP-9i enhanced the thinning of the INL, the loss of Calbindin D-28k-positive cells and Syntaxin-positive amacrine cells (ACs) in the INL and decreased levels of Calbindin D-28k protein, while leaving the outer nuclear layer (ONL) unchanged. In addition, MMP-9i led to a minor increase in the number of BrdU positive cells that did not express GS in the INL. Collectively, these results revealed that the inhibition of MMP-9 activity facilitated AC loss and promoted the generation of MGC-derived cells in ouabain-treated retinas, which indicates that treating retinal diseases with drugs that inhibit MMP-9 activity should be considered with caution.
['Li|Yan|Y|', 'Zhou|Guo-Min|GM|']
D025042:Amacrine Cells D000818:Animals D017209:Apoptosis D016923:Cell Death D049109:Cell Proliferation D004195:Disease Models, Animal D005260:Female D007511:Ischemia D020780:Matrix Metalloproteinase 9 D061965:Matrix Metalloproteinase Inhibitors D009457:Neuroglia D010042:Ouabain D051381:Rats D017207:Rats, Sprague-Dawley D012160:Retina D012162:Retinal Degeneration D012165:Retinal Ganglion Cells D012171:Retinal Vessels
MMP-9 Amacrine cell Retinal ischemia Müller glial cell Ouabain