The exit strategy: Pharmacological modulation of extracellular matrix production and deposition for better aqueous humor drainage.
Primary open angle glaucoma (POAG) is an optic neuropathy and an irreversible blinding disease. The etiology of glaucoma is not known but numerous risk factors are associated with this disease including aging, elevated intraocular pressure (IOP), race, myopia, family history and use of steroids. In POAG, the resistance to the aqueous humor drainage is increased leading to elevated IOP. Lowering the resistance and ultimately the IOP has been the only way to slow disease progression and prevent vision loss. The primary drainage pathway comprising of the trabecular meshwork (TM) is made up of relatively large porous beams surrounded by extracellular matrix (ECM). Its juxtacanalicular tissue (JCT) or the cribriform meshwork is made up of cells embedded in dense ECM. The JCT is considered to offer the major resistance to the aqueous humor outflow. This layer is adjacent to the endothelial cells forming Schlemm's canal, which provides approximately 10% of the outflow resistance. The ECM in the TM and the JCT undergoes continual remodeling to maintain normal resistance to aqueous humor outflow. It is believed that the TM is a major contributor of ECM proteins and evidence points towards increased ECM deposition in the outflow pathway in POAG. It is not clear how and from where the ECM components emerge to hinder the normal aqueous humor drainage. This review focuses on the involvement of the ECM in ocular hypertension and glaucoma and the mechanisms by which various ocular hypotensive drugs, both current and emerging, target ECM production, remodeling, and deposition.
Department of Ophthalmology and Visual Science, Case Western Reserve University, Wearn Building 411, 11100 Euclid Avenue, Cleveland 44106, United States.
Padmanabhan P
PP
Pattabiraman
Department of Ophthalmology and Visual Science, Case Western Reserve University, Wearn Building 411, 11100 Euclid Avenue, Cleveland 44106, United States. Electronic address: cbt22@case.edu.
Carol B
CB
Toris
D000818:Animals; D001082:Aqueous Humor / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005128:Eye Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006801:Humans
Aqueous humor outflow; Extracellular matrix; Fibrosis; Intraocular pressure; Primary open angle glaucoma; Trabecular meshwork