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Discovering Matrix Metalloproteinases and How They Could Lead to Future Glaucoma Treatments

Posted on March 02, 2017 by Glaucoma Research Foundation
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Matrix metalloproteinases (or MMPs) may sound like something out of a sci-fi story, but they’re a real-life family of enzymes—the metzincin superfamily—that thrive inside the human body. Normally these super enzymes are friendly and essential for your health, but they can contribute to serious problems like glaucoma. Therefore, researchers are hard at work trying to determine the precise role of matrix metalloproteinases in glaucoma, and how that role can be utilized to come up with new and better glaucoma treatment therapies.

Matrix Metalloproteinases: Sentinels of Cells

To understand the power of matrix metalloproteinases, you have to know about the extracellular matrix (ECM). The ECM consists of super-strong collagen, elastic connective tissue and a variety of other specialized proteins, which weave together to form a three-dimensional network that surrounds individual cells throughout the body. It multitasks to accomplish several jobs. One role is structural—it supports and cushions cells—but it also regulates biochemical reactions that determine cellular growth and functioning.

The ECM is a dynamic network that constantly sheds old or damaged tissue and replaces it with new tissue. That’s where MMPs come into the picture. They’re responsible for breaking down the ECM tissues that need to be replaced. The interaction between MMPs and the ECM determines whether cells thrive and function properly, or stop working and die.

Over more than 40 years of research, scientists have discovered that MMPs help regulate such vital activities as the immune response, inflammation, and the growth of new blood vessels.1 When MMPs get out of balance—when the amount of enzyme is unusually high or low—they contribute to a variety of serious health problems, including the development of glaucoma.

Inside the Eye: Matrix Metalloproteinases and Glaucoma

MMPs are typically low in healthy eyes, but their presence is noticeably higher in glaucoma—a fact that piqued interest and motivated researchers to study the relationship between MMPs and glaucoma. One of the first things they learned was that MMPs affect intraocular pressure through their role in remodeling the ECM in the trabecular meshwork, which is a structure near the iris that maintains normal eye pressure by draining fluids.2

Glaucoma experts then began to explore the potential role of MMPs in the death of retinal ganglion cells (RGCs), the nerve cells s responsible for carrying visual signals out of the retina and into the optic nerve on the way to the brain. Following multiple complex studies, they learned that high levels of one specific MMP—MMP-9—contributed to RGC degeneration. This is an extraordinary discovery that demands more work to figure out how it happens and what that means for glaucoma.

Another association between glaucoma and MMPs may come from their influence on a second mesh-like structure in the eye, the lamina cribrosa. As the optic nerve leaves the eye, the individual RGC fibers pass through small openings in the lamina cribrosa. Higher-than-normal levels of MMPs may cause imbalanced remodeling of the lamina cribrosa’s ECM, which could contribute to the death of RGCs by damaging their fibers. However, it will take many additional years of research to verify the molecular steps and biochemicals involved in that process.

Researchers have several solid theories about which biochemicals might trigger abnormal MMP activity in different parts of the eye, so they have good leads to follow. But it will take time because this is groundbreaking work without a map to guide the way. If they can accomplish the goal of identifying key biochemicals, they’ll have new therapeutic targets for future glaucoma treatment.

It is research like this, funded by people like you, that gives hope to the glaucoma community. Your generous donation to Glaucoma Research Foundation goes to support researchers developing the next generation of glaucoma treatments.

1 “Biological Role of Matrix Metalloproteinases: A Critical Balance,” July 2011, http://erj.ersjournals.com/content/38/1/191

2 “MMPs in the Neuroretina and Optic Nerve: Modulators of Glaucoma Pathogenesis and Repair?” March 2014, http://iovs.arvojournals.org/article.aspx?articleid=2190449

Last reviewed on March 06, 2017

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