Aberrant Collagen Composition of the Trabecular Meshwork Results in Reduced Aqueous Humor Drainage and Elevated IOP in MMP-9 Null Mice.
OBJECTIVE
Homeostatic turnover of the trabecular meshwork extracellular matrix (ECM) is essential to regulate aqueous humor outflow and to maintain intraocular pressure homeostasis. In this study, we evaluated aqueous humor turnover, intraocular pressure, and trabecular meshwork organization in MMP-9 null mice.


METHODS
Intraocular pressure and aqueous humor turnover were measured in MMP-9 null versus wild-type mice. Morphology of the anterior segment of the eye, with special attention to the structural organization of the trabecular meshwork, was investigated by means of optical coherence tomography, light microscopy, and transmission electron microscopy. Furthermore, using quantitative real-time polymerase chain reaction and immunostainings, we evaluated the ECM composition of the trabecular meshwork. Finally, the integrity and function of the retina and optic nerve were assessed, via optical coherence tomography, histologic techniques, and optomotor testing.


RESULTS
MMP-9 null mice displayed early-onset ocular hypertension and reduced aqueous humor turnover. While transmission electron microscopic analysis did not reveal any abnormalities in the cellular organization of the trabecular meshwork, detailed investigation of collagen expression indicated that there is an aberrant trabecular meshwork ECM composition in MMP-9 null mice. Notably, at the age of 13 months, no glaucomatous neurodegeneration was seen in MMP-9 null mice.


CONCLUSIONS
Our observations corroborate MMP-9 as an important remodeler of the collagenous composition of the trabecular meshwork and provide evidence for a causal link between MMP-9 deficiency, trabecular meshwork ultrastructure, and ocular hypertension.
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium 2Laboratory of Ophthalmology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Lies
L
De Groef
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Lien
L
Andries
Department of Pathology and Molecular Medicine, McMaster University Health Science Centre, Hamilton, Ontario, Canada.
Anuja
A
Siwakoti
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Emiel
E
Geeraerts
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Ilse
I
Bollaerts
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Lut
L
Noterdaeme
ThromboGenics NV, Heverlee, Belgium.
Isabelle
I
Etienne
Centre for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium 6Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.
Anna-Pia
AP
Papageorgiou
Laboratory of Ophthalmology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Ingeborg
I
Stalmans
Laboratory of Socioecology and Social Evolution, Ecology, Evolution and Biodiversity Conservation Section, Department of Biology, KU Leuven, Leuven, Belgium.
Johan
J
Billen
Department of Pathology and Molecular Medicine, McMaster University Health Science Centre, Hamilton, Ontario, Canada.
Judith A
JA
West-Mays
Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
Lieve
L
Moons
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D007429:Intraocular Pressure / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009798:Ocular Hypertension / Q000378:metabolism* / Q000503:physiopathology; D009900:Optic Nerve / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D014129:Trabecular Meshwork / Q000378:metabolism*
D020780:Matrix Metalloproteinase 9