MMPs in the Trabecular Meshwork: Promising Targets for Future Glaucoma Therapies?

Abstract

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.

The Association of Nailfold Capillaroscopy with Systemic Matrix Metalloproteinase-9 Concentration in Normal-Tension Glaucoma

“…34 Recently, Robertson and West-Mays 35 reported an increased IOP in MMP-9-deficient mice, and suggested an important role for MMP-9 in maintaining IOP and ECM remodeling in the anterior angle. However, the present study found no significant correlation of IOP with plasma MMP-9 concentration.…”

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

“…MMP proteins are often upregulated in glaucomatous AH; however, the activity of these proteins is reduced in comparison to cataract controls, likely reflective of MMP:TIMP imbalance [92,[96][97][98]. Perfusion of ocular tissues with MMPs or MMP-activating compounds results in increased outflow facility, possibly the most convincing demonstration of ECM involvement in regulating outflow resistance [99][100][101][102]. Furthermore, recent studies on ECM characteristics, such as stiffness resulting from crosslinking, or caveolin-mediated matrix endocytosis, also highlight ECM influence on outflow facility [103,104].…”

Expression of Matrix Metalloproteinases in Lacrimal Fluid and Gene Polymorphism of Complement Factor H (Cfh) in Patients With Primary Open-Angle Glaucoma

“…Морфологиче-ские исследования структур глаза человека и жи-вотных подтверждают их гиперэкспрессию при глаукоме в трабекулярной сети [7,9,11], в шлем-мове канале [23], в сетчатке [8,10], решетчатой пластине склеры [36] и диске зрительного не-рва [19]. Предполагают наличие причинно-след-ственной связи между уровнем ММП и реакци-ями ремоделирования ДЗН и сетчатки.…”