Optic nerve ligation leads to astrocyte-associated matrix metalloproteinase-9 induction in the mouse retina.
Ischemic damage results in irreversible ganglion cell loss in the retina. While the mechanisms underlying ischemia-induced ganglion cell loss are not clearly understood, we have recently reported that ischemia, induced by optic nerve ligation, results in increased nerve fiber layer-associated matrix metalloproteinase-9 (MMP-9) induction and loss of ganglion cells from the retina. This study was conducted to determine the cellular source of MMP-9 using antibodies against MMP-9 and various cell types in the inner retina. The results presented in this study show that optic nerve ligation leads to induction of MMP-9 and activation of astrocytes. Double labeling studies using antibodies against MMP-9 and GFAP showed a greater overlap of MMP-9 with GFAP, compared to antibodies against glutamine synthetase and MMP-9 which showed no overlapping, suggesting that activated astrocytes contribute to MMP-9 expression in the retina. Further, double labeling studies using antibodies against von Willebrand factor and MMP-9 or Mac-1 and MMP-9 showed no overlapping of MMP-9 with any antibodies indicating that endothelial cells and microglial cells are not the principal source of MMP-9 in the retina following optic nerve ligation.
Zhang
Xu
X
Eye Research Institute of Oakland University, 409 Dodge Hall, Rochester, MI 48309, USA.
Cheng
Mei
M
Chintala
Shravan K
SK
D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D007150:Immunohistochemistry; D008026:Ligation; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051379:Mice; D018613:Microscopy, Confocal; D018917:Optic Neuropathy, Ischemic / Q000201:enzymology*; D012160:Retina / Q000201:enzymology*
D005904:Glial Fibrillary Acidic Protein; D020780:Matrix Metalloproteinase 9; D005974:Glutamate-Ammonia Ligase