MMP‐9 null mice display elevated IOP due to reduced aqueous humor drainage from the trabecular meshwork

Purpose Aqueous humor outflow resistance depends on a complex equilibrium of extracellular matrix biosynthesis versus proteolysis in the trabecular meshwork. Several members of the MMP family, including MMP ‐9, are essential to the regulation of aqueous humor outflow resistance, i.e . to intraocular pressure ( IOP ) homeostasis. Here, we characterized the baseline ocular phenotype of MMP ‐9 null mice, with emphasis on the dysregulation of IOP homeostasis. Methods MMP ‐9 null and wild type mice, from 3 to 13 months of age, were studied. IOP and central corneal thickness were measured via rebound tonometry and pachymetry, resp. Anterior chamber morphology and trabecular meshwork organization were studied (1) in vivo with OCT , (2) via light microscopy and (3) by means of transmission electron microscopy ( TEM ), and its collagen composition was studied using Sirius Red and immunostainings. Integrity of the retina and optic nerve were evaluated with OCT and histological stainings on tissue sections and retinal flatmounts. Results MMP ‐9 null mice present with early‐onset ocular hypertension, and fluorophotometric measurements of aqueous humor turnover revealed a reduced aqueous humor drainage. While OCT , light microscopy and TEM analysis did not disclose any abnormalities in the cellular organization of the trabecular meshwork, collagen staining indicated that there is an aberrant extracellular matrix composition in MMP ‐9 null mice. Remarkably, the observed IOP elevation in MMP ‐9 null mice did not result in a glaucomatous phenotype at the level of the retina and optic nerve at the ages studied. Conclusions Our observations corroborate the role of MMP ‐9 as an important remodeler of the trabecular meshwork, and evidence for a causal link between MMP ‐9 deficiency, trabecular meshwork composition and IOP elevation is revealed.