title: Interaction of cochlin and mechanosensitive channel TREK-1 in trabecular meshwork cells influences the regulation of intraocular pressure.
abstract: In the eye, intraocular pressure (IOP) is tightly regulated and its persistent increase leads to ocular hypertension and glaucoma. We have previously shown that trabecular meshwork (TM) cells might detect aqueous humor fluid shear stress via interaction of the extracellular matrix (ECM) protein cochlin with the cell surface bound and stretch-activated channel TREK-1. We provide evidence here that interaction between both proteins are involved in IOP regulation. Silencing of TREK-1 in mice prevents the previously demonstrated cochlin-overexpression mediated increase in IOP. Biochemical and electrophysiological experiments demonstrate that high shear stress-induced multimeric cochlin produces a qualitatively different interaction with TREK-1 compared to monomeric cochlin. Physiological concentrations of multimeric but not monomeric cochlin reduce TREK-1 current. Results presented here indicate that the interaction of TREK-1 and cochlin play an important role for maintaining IOP homeostasis. [Corrected].
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.|Department of Biochemistry and Molecular Biology, University of Miami, Miami, USA.
authors.forename: Teresia A
authors.initials: TA
authors.lastname: Carreon
authors.affiliation: Department of Biomedicine, University of Barcelona, Barcelona, Spain.|Institut d'Investigaciones Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Castellanos
authors.affiliation: Department of Biomedicine, University of Barcelona, Barcelona, Spain.|Institut d'Investigaciones Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.identifier: 0000-0002-6154-8323
authors.initials: X
authors.lastname: Gasull
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA. Sbhattacharya@med.miami.edu.|Department of Biochemistry and Molecular Biology, University of Miami, Miami, USA. Sbhattacharya@med.miami.edu.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Bhattacharya