MMPs in Glaucoma

Judith West-Mays, PhD
McMaster University (Hamilton, Canada)
Year Awarded:
2008
Grant Duration:
April 1, 2008 to November 30, 2010
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2008127
Award Type:
Standard
Award Region:
International
Judith West-Mays, PhD

The Roles of MMPs in TGFbeta induced Glaucoma

Summary

Researchers on this project will examine how eyes with glaucoma differ molecularly from normal eyes. They will specifically focus on the roles of MMPs, which are proteins that limit scarring in the eye. They hypothesize that increasing the activity of MMPs may be a treatment option for glaucoma symptoms.

Details

The goal of our research is to determine what differentiates an eye displaying glaucoma symptoms from a normal eye. The glaucoma eye is different in the sense that it expresses different concentrations and combinations of molecules that are typically found in a normal eye. Some of these molecules are involved in formation of scar tissue (TGF) or breakdown of scar tissue (MMPs). We wish to determine how manipulation of MMPs can influence the development of scarring in the eye, which can lead to glaucoma. Also, we wish to establish the time at which these molecules begin to differ in quantity, which may explain the worsening of symptoms characteristic of glaucoma over time. Previously, no one has attempted to determine the role of MMPs in glaucoma induced by TGF and research has shown that halting the activity of MMPs may be beneficial in reducing the severity of ocular disorders. Characterizing MMP activity in an animal model where TGF is artificially in abundance is important because glaucoma is often characterized by increased levels of TGF. It is crucial that the roles of MMPs are characterized in a glaucoma-like environment. If our predictions hold true for the role of MMPs in glaucoma, MMP inhibition may be an excellent treatment option for some glaucoma patients. Additionally, if a timeline for disease progression in the TGF model is successfully documented, it will greatly facilitate the generation of new methods of treatment, as various therapies could be implemented at a time known to be prior to symptom expression and the effects of the treatment monitored. First, we wish to determine a time prior to, during and post glaucoma symptom expression that will allow for these various timepoints to be studied and their importance to symptom progression. Secondly, we wish to determine how and where MMPs are involved in this model of glaucoma. Finally, we wish to determine if inhibition of MMPs will prevent the animals from developing glaucoma. - This research seeks to determine what differentiates an eye with glaucoma symptoms from a normal eye. In glaucoma, the eye expresses different concentrations and combinations of molecules than typically found in a normal eye. Some of these molecules are involved in the formation or breakdown of scar tissue. Matrix metalloproteinases (MMPs) are molecules involved in the breakdown of scar tissue; transforming growth factor beta (TGF) is associated with scar tissue formation. The researchers will manipulate MMPs to determine their effect on scarring in the eye, which can lead to glaucoma. The scientists also want to establish when the MMPs begin to differ in quantity, which may explain worsening glaucoma symptoms. If predictions hold true for the role of MMPs in glaucoma, MMP inhibition may be an excellent treatment option for some glaucoma patients. Additionally, if a timeline for disease progression can be established, it will greatly facilitate the generation of new treatment methods before symptoms occur.

Publications

Robertson JV, Golesic E, Gauldie J, West-Mays JA. Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats. Invest Ophthalmol Vis Sci. 2010 Jan;51(1):308-18.  

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