MMPs in the trabecular meshwork: promising targets for future glaucoma therapies?

Glaucoma is one of the world's most common blinding diseases, affecting more than 60 million people worldwide. Although the disease presents as a neurodegenerative disorder affecting retinal ganglion cell axons in the optic nerve and their somata in the retina, the elicitors of this optic neuropathy are often located outside the neuroretina. Disturbances in aqueous humor outflow, leading to ocular hypertension, are considered to be the major risk factor for the development of glaucoma. Although an amplitude of pharmacological and surgical measures is available to lower IOP in glaucoma patients, these are not always sufficient to halt the disease. Multiple surveys in glaucoma patients, as well as in vitro studies in anterior segment explant or cell cultures, reported changes in the expression and activity of several matrix metalloproteinases (MMPs) in the aqueous humor and trabecular meshwork, in response to elevated IOP. In this review, we describe MMPs as important modulators of aqueous humor outflow, functioning in a feedback mechanism that continuously remodels the trabecular meshwork extracellular matrix composition in order to maintain a stable outflow resistance and IOP. We review the evidence for the involvement of MMPs in glaucoma disease onset and investigate their potential as therapeutic targets for the development of future glaucoma therapies.