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.
Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Fudan University, 200032 Shanghai, China. Electronic address: liyan@shmu.edu.cn.
Yan
Y
Li
Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Fudan University, 200032 Shanghai, China. Electronic address: loverretina@gmail.com.
Guo-Min
GM
Zhou
D025042:Amacrine Cells / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007511:Ischemia / Q000150:complications; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000201:enzymology; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D012171:Retinal Vessels
D061965:Matrix Metalloproteinase Inhibitors; D010042:Ouabain; D020780:Matrix Metalloproteinase 9
Amacrine cell; MMP-9; Müller glial cell; Ouabain; Retinal ischemia