Matrix metalloproteinases (MMPs) are known to be the mediators of extracellular matrix remodeling. Increased levels of matrix metalloproteinases, particularly MMP-9, have been found in the aqueous humor of patients with glaucoma. However the exact role of MMP-9 in glaucomatous changes is not understood. Previous results from the West-Mays’ lab indicated that MMP-9 deficient (knockout - KO) mice exhibit elevated IOP, in the absence of distinct morphological changes in the anterior chamber.
In the current thesis, I investigated whether the elevated IOP in MMP-9KO mice leads to RGC death. Wild type and KO littermates at different age groups: 2-3 months, 3-4 months, 6-8 and 9-12 months were studied. IOP was measured using TonoLab rebound tonometer. My results demonstrated that IOP was significantly increased in MMP-9KO mice compared to control littermates at all ages examined. To investigate if the elevated IOP was due to a difference in central corneal thickness (CCT), CCT measurements were made between WT and KO mice using ultrasound pachymeter. There was no difference in CCT demonstrating that the elevated IOP observed in MMP-9KO mice was not related to changes in corneal thickness. To determine whether the elevated IOP led to RGC death, the animals were sacrificed, eyes were enucleated and retinas (n=4) from both WT and KO animals were dissected and stained with Brn-3a antibody. Additional eyes were harvested from both WT and KO mice for histological and immunofluorescence studies. I found no observable difference in Brn3a+ RGC count between MMP9-WT and KO mice. Furthermore, no difference in retinal morphology, glial reactivity and laminin expression between WT and KO mice was observed. In the future it will be important to investigate whether elevated IOP in the MMP-9KO mice leads to optic nerve axonal loss and further investigate the possibility that the MMP-9KO retina is neuroprotected. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16035 |
| Date | January 2014 |
| Creators | Siwakoti, Anuja |
| Contributors | West-Mays, Judith, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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