title: The role of matricellular proteins in glaucoma.
abstract: Glaucoma is an optic neuropathy affecting approximately 60million people worldwide and is the second most common cause of irreversible blindness. Elevated intraocular pressure (IOP) is the main risk factor for developing glaucoma and is caused by impaired aqueous humor drainage through the trabecular meshwork (TM) and Schlemm's canal (SC). In primary open angle glaucoma (POAG), this elevation in IOP in turn leads to deformation at the optic nerve head (ONH) specifically at the lamina cribrosa (LC) region where there is also a deposition of extracellular matrix (ECM) molecules such as collagen and fibronectin. Matricellular proteins are non-structural secreted glycoproteins that help cells communicate with their surrounding ECM. This family of proteins includes connective tissue growth factor (CTGF), also known as CCN2, thrombospondins (TSPs), secreted protein acidic and rich in cysteine (SPARC), periostin, osteonectin, and Tenascin-C and -X and other ECM proteins. All members appear to play a role in fibrosis and increased ECM deposition. Most are widely expressed in tissues particularly in the TM and ONH and deficiency of TSP1 and SPARC have been shown to lower IOP in mouse models of glaucoma through enhanced outflow facility. The role of these proteins in glaucoma is emerging as some have an association with the pathophysiology of the TM and LC regions and might therefore be potential targets for therapeutic intervention in glaucoma.
authors.affiliation: UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Dept. of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland. Electronic address: deborahmwallace1@gmail.com.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Wallace
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Murphy-Ullrich
authors.affiliation: Department of Ophthalmology, Center for Ocular Biomechanics and Biotransport, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: J Crawford
authors.initials: JC
authors.lastname: Downs
authors.affiliation: UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland; Dept. of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005901:Glaucoma / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D015676:Osteonectin / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D015676:Osteonectin; C082838:Postn protein, mouse; C578250:SPARC protein, mouse; D019699:Thrombospondins; D055513:Connective Tissue Growth Factor
keywords: CTGF; Fibrosis; Glaucoma; Matricellular; Periostin; SPARC; TGFβ; TSP1