May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
MMP-9 Knockout in a Mouse Model of Glaucoma
Author Affiliations & Notes
  • F.-L. Silver
    Ophthalmology, Duke University Eye Center, Durham, North Carolina
  • L. Kasmala
    Ophthalmology, Duke University Eye Center, Durham, North Carolina
  • S. J. McKinnon
    Ophthalmology, Duke University Eye Center, Durham, North Carolina
  • Footnotes
    Commercial Relationships F. Silver, None; L. Kasmala, None; S.J. McKinnon, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4940. doi:
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      F.-L. Silver, L. Kasmala, S. J. McKinnon; MMP-9 Knockout in a Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4940.

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Abstract

Purpose:: It has been shown that matrix metalloproteinase-9 (MMP-9) is involved in loss of ganglion cells, while knockout of MMP-9 protects against these changes. This led to our interest in determining whether the Morrison model could be adapted to investigate the possible neuroprotective effects of MMP-9 knockout in mice.

Methods:: 30 MMP-9 KO mice and 30 matched controls were obtained from Jackson Labs and elevated intraocular pressure was induced through injection of hypertonic saline into the episcleral vessels using the Morrison model. We injected the right eye only and used the left eye as a control in each animal. IOP was measured weekly in conscious mice using a TonoLab rebound tonometer. When the group average change of IOP was greater than 600 mmdays, we collected control and treated eyes under sedation. Optic nerve cross sections were stained with toluidine blue. Axon counts were obtained in a masked fashion for both control and treated eyes using the Zeiss KS400 Image Analysis system and % axon survival was calculated and tested for significance with the Student’s t-test.

Results:: Elevated intraocular pressure was successfully induced in all animals in the treated right eye. In WT animals, axon counts were decreased in treated eyes (avg. 41,219, p=0.0016), whereas in MMP-9 KO animals, axon counts were not decreased in treated eyes (avg. 52,434, p=0.1585).

Conclusions:: As previously shown by others, KO of MMP-9 shows some neuroprotective effect in the setting of elevated IOP. We have shown that the Morrison model can be successfully adapted to use in mice in our hands and will be a useful tool for further investigating the pathophysiology of MMP-9 involvement in axon loss in glaucoma.

Keywords: intraocular pressure • ganglion cells • neuroprotection 
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