title: Elevated intraocular pressure induces Rho GTPase mediated contractile signaling in the trabecular meshwork.
abstract: Rho GTPase regulated contractile signaling in the trabecular meshwork (TM) has been shown to modulate aqueous humor (AH) outflow and intraocular pressure (IOP). To explore whether elevated IOP, a major risk factor for primary open angle glaucoma (POAG) influences Rho GTPase signaling in the TM, we recorded AH outflow in enucleated contralateral porcine eyes perfused for 4-5 h at either 15 mm or 50 mm Hg pressure. After perfusion, TM tissue extracted from perfused eyes was evaluated for the activation status of Rho GTPase, myosin light chain (MLC), myosin phosphatase target substrate 1 (MYPT1), myristoylated alanine-rich C-kinase substrate (MARCKS) and paxillin. Eyes perfused at 50 mm Hg exhibited a significant decrease in AH outflow facility compared with those perfused at 15 mm Hg. Additionally, TM tissue from eyes perfused at 50 mm Hg revealed significantly increased levels of activated RhoA and phosphorylated MLC, MYPT1, MARCKS and paxillin compared to TM tissue derived from eyes perfused at 15 mm Hg. Taken together, these observations indicate that elevated IOP-induced activation of Rho GTPase-dependent contractile signaling in the TM is associated with increased resistance to AH outflow through the trabecular pathway, and demonstrate the sensitivity of Rho GTPase signaling to mechanical force in the AH outflow pathway.
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Padmanabhan P
authors.initials: PP
authors.lastname: Pattabiraman
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. Electronic address: p.rao@dm.duke.edu.
authors.forename: P Vasantha
authors.initials: PV
authors.lastname: Rao
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007429:Intraocular Pressure / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009798:Ocular Hypertension / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D013552:Swine; D014129:Trabecular Meshwork / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018994:Myosin Light Chains; D051419:Paxillin; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D043263:Myosin-Light-Chain Phosphatase; D020742:rhoA GTP-Binding Protein
keywords: Intraocular pressure; Mechanotransduction; Outflow resistance; Rho GTPase; Trabecular meshwork