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J. Biol. Chem., Vol. 277, Issue 49, 47461-47468, December 6, 2002
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From the Loss of retinal ganglion cells is the final end
point in blinding diseases of the optic nerve such as glaucoma. To
enable the use of mouse genetics to investigate mechanisms underlying ganglion cell loss, we adapted an experimental model of optic nerve
ligation to the mouse and further characterized post-surgical outcome.
We made the novel finding that apoptosis of retinal ganglion cells
correlates with specific degradation of laminin from the underlying
inner limiting membrane and an increase in gelatinolytic metalloproteinase activity. These changes co-localize with a specific increase in levels of the matrix metalloproteinase, gelatinase B (GelB;
MMP-9). Using a transgenic mouse line harboring a reporter gene driven
by the GelB promoter, we further show that increased GelB is controlled
by activation of the GelB promoter. These findings led us to
hypothesize that GelB activity plays a role in ganglion cell death and
degradation of laminin. Applying the genetic approach, we demonstrate
that GelB-deficient mice are protected against these pathological
changes. This is the first report demonstrating a causal connection
between GelB activity and pathological changes to the inner retina
after optic nerve ligation.
Deficiency in Matrix Metalloproteinase Gelatinase B (MMP-9)
Protects against Retinal Ganglion Cell Death after Optic Nerve
Ligation*
§¶,,
, and**
Eye Research Institute, Oakland University,
Rochester, Michigan 48309, Bascom Palmer Eye Institute,
University of Miami School of Medicine, Miami, Florida 33101, and
§ New England Eye Center, Tufts University School of
Medicine and the Tufts Center for Vision Research,
Boston, Massachusetts 02111
*
This work was supported by NEI, National Institutes of
Health Project Grants EY13643 and EY12651, NEI Center Grant EY13078, and by the Massachusetts Lions Eye Research Fund Inc. and Research to
Prevent Blindness.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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