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Abstract #8524 Published in IGR 5-1
Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation
Chintala SK; Zhang X; Austin JS; Fini MEJournal of Biological Chemistry 2002; 277: 47461-47468
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, the authors adapted an experimental model of optic nerve ligation to the mouse and further characterized post-surgical outcome. They 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, the authors further show that increased GelB is controlled by activation of the GelB promoter. These findings led them to hypothesize that GelB activity plays a role in ganglion cell death and degradation of laminin. Applying the genetic approach, they 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.
Dr. S.K. Chintala, Eye Research Institute, 409 Dodge Hall, Oakland University, Rochester, MI 48309, USA. Chintala@oakland.edu
Classification:
11.9 Gene therapy (Part of: 11 Medical treatment)
