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  • 1
    Online Resource
    Online Resource
    Effects of Novel Ethacrynic Acid Derivatives on Human Trabecular Meshwork Cell Shape, Actin Cytoskeletal Organization, and Transcellular Fluid Flow
    Pharmaceutical Society of Japan ; 2005
    In:  Biological and Pharmaceutical Bulletin Vol. 28, No. 12 ( 2005), p. 2189-2196
    Details
    In: Biological and Pharmaceutical Bulletin, Pharmaceutical Society of Japan, Vol. 28, No. 12 ( 2005), p. 2189-2196
    Type of Medium: Online Resource
    ISSN: 0918-6158 , 1347-5215
    URL: Article
    DOI: 10.1248/bpb.28.2189
    Language: English
    Publisher: Pharmaceutical Society of Japan
    Publication Date: 2005
    detail.hit.zdb_id: 2029846-8
    SSG: 12
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Ankyrin-B in lens architecture and biomechanics: Just not tethering but more
    Informa UK Limited ; 2016
    In:  BioArchitecture Vol. 6, No. 2 ( 2016-03-03), p. 39-45
    Details
    In: BioArchitecture, Informa UK Limited, Vol. 6, No. 2 ( 2016-03-03), p. 39-45
    Type of Medium: Online Resource
    ISSN: 1949-0992 , 1949-100X
    URL: Article
    DOI: 10.1080/19490992.2016.1156284
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2628854-0
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  • 3
    Online Resource
    Online Resource
    Calponin-3 deficiency augments contractile activity, plasticity, fibrogenic response and Yap/Taz transcriptional activation in lens epithelial cells and explants
    Springer Science and Business Media LLC ; 2020
    In:  Scientific Reports Vol. 10, No. 1 ( 2020-01-28)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-01-28)
    Abstract: The transparent ocular lens plays a crucial role in vision by focusing light on to the retina with loss of lens transparency leading to impairment of vision. While maintenance of epithelial phenotype is recognized to be essential for lens development and function, knowledge of the identity of different molecular mechanisms regulating lens epithelial characteristics remains incomplete. This study reports that CNN-3, the acidic isoform of calponin, an actin binding contractile protein, is expressed preferentially and abundantly relative to the basic and neutral isoforms of calponin in the ocular lens, and distributes predominantly to the epithelium in both mouse and human lenses. Expression and MEKK1-mediated threonine 288 phosphorylation of CNN-3 is induced by extracellular cues including TGF-β2 and lysophosphatidic acid. Importantly, siRNA-induced deficiency of CNN3 in lens epithelial cell cultures and explants results in actin stress fiber reorganization, stimulation of focal adhesion formation, Yap activation, increases in the levels of α-smooth muscle actin, connective tissue growth factor and fibronectin, and decreases in E-cadherin expression. These results reveal that CNN3 plays a crucial role in regulating lens epithelial contractile activity and provide supporting evidence that CNN-3 deficiency is associated with the induction of epithelial plasticity, fibrogenic activity and mechanosensitive Yap/Taz transcriptional activation.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-58189-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 4
    Online Resource
    Online Resource
    Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-07-22)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-07-22)
    Abstract: The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-94391-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    Autotaxin-Lysophosphatidic Acid Axis Is a Novel Molecular Target for Lowering Intraocular Pressure
    Public Library of Science (PLoS) ; 2012
    In:  PLoS ONE Vol. 7, No. 8 ( 2012-8-20), p. e42627-
    Details
    In: PLoS ONE, Public Library of Science (PLoS), Vol. 7, No. 8 ( 2012-8-20), p. e42627-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0042627
    DOI: 10.1371/journal.pone.0042627.s001
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2012
    detail.hit.zdb_id: 2267670-3
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  • 6
    Online Resource
    Online Resource
    Lysophosphatidic Acid Induces ECM Production via Activation of the Mechanosensitive YAP/TAZ Transcriptional Pathway in Trabecular Meshwork Cells
    Association for Research in Vision and Ophthalmology (ARVO) ; 2018
    In:  Investigative Opthalmology & Visual Science Vol. 59, No. 5 ( 2018-04-09), p. 1969-
    Details
    In: Investigative Opthalmology & Visual Science, Association for Research in Vision and Ophthalmology (ARVO), Vol. 59, No. 5 ( 2018-04-09), p. 1969-
    Type of Medium: Online Resource
    ISSN: 1552-5783
    URL: Article
    DOI: 10.1167/iovs.17-23702
    Language: English
    Publisher: Association for Research in Vision and Ophthalmology (ARVO)
    Publication Date: 2018
    detail.hit.zdb_id: 2009858-3
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  • 7
    Online Resource
    Online Resource
    Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Cell Physiology Vol. 295, No. 5 ( 2008-11), p. C1057-C1070
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 295, No. 5 ( 2008-11), p. C1057-C1070
    Abstract: Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated actomyosin organization, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active mutant of RhoA (RhoAV14). Organ-cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 exhibited a pronounced contractile morphology, increased actin stress fibers, and focal adhesions and increased levels of phosphorylated myosin light chain (MLC), collagen IV, fibronectin, and laminin. cDNA microarray analysis of RNA extracted from RhoAV14-expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins, and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of MLC, paxillin, and focal adhesion kinase and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the actomyosin assembly, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00481.2007
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Effects of the New Ethacrynic Acid Derivative SA9000 on Intraocular Pressure in Cats and Monkeys
    Pharmaceutical Society of Japan ; 2004
    In:  Biological and Pharmaceutical Bulletin Vol. 27, No. 7 ( 2004), p. 1019-1024
    Details
    In: Biological and Pharmaceutical Bulletin, Pharmaceutical Society of Japan, Vol. 27, No. 7 ( 2004), p. 1019-1024
    Type of Medium: Online Resource
    ISSN: 0918-6158 , 1347-5215
    URL: Article
    DOI: 10.1248/bpb.27.1019
    Language: English
    Publisher: Pharmaceutical Society of Japan
    Publication Date: 2004
    detail.hit.zdb_id: 2029846-8
    SSG: 12
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    The role of calcium-independent phospholipase A 2 γ in modulation of aqueous humor drainage and Ca 2+ sensitization of trabecular meshwork contraction
    American Physiological Society ; 2012
    In:  American Journal of Physiology-Cell Physiology Vol. 302, No. 7 ( 2012-04-01), p. C979-C991
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 302, No. 7 ( 2012-04-01), p. C979-C991
    Abstract: The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A 2 (iPLA 2 ), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA 2 γ specific) and (S)-bromoenol lactone (S-BEL, iPLA 2 β specific). Immunohistochemical analysis revealed intense staining for both iPLA 2 β and γ isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA 2 γ by R-BEL or small interfering RNA-mediated silencing of iPLA 2 γ expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA 2 γ plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA 2 γ on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00396.2011
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2012
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells
    American Physiological Society ; 2010
    In:  American Journal of Physiology-Cell Physiology Vol. 298, No. 3 ( 2010-03), p. C749-C763
    Details
    In: American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 298, No. 3 ( 2010-03), p. C749-C763
    Abstract: Elevated intraocular pressure arising from impaired aqueous humor drainage through the trabecular pathway is a major risk factor for glaucoma. To understand the molecular basis for Rho GTPase-mediated resistance to aqueous humor drainage, we investigated the possible interrelationship between actomyosin contractile properties and extracellular matrix (ECM) synthesis in human trabecular meshwork (TM) cells expressing a constitutively active form of RhoA (RhoAV14). TM cells expressing RhoAV14 exhibited significant increases in fibronectin, tenascin C, laminin, α-smooth muscle actin (α-SMA) levels, and matrix assembly in association with increased actin stress fibers and myosin light-chain phosphorylation. RhoAV14-induced changes in ECM synthesis and actin cytoskeletal reorganization were mimicked by lysophosphatidic acid and TGF-β 2 , known to increase resistance to aqueous humor outflow and activate Rho/Rho kinase signaling. RhoAV14, lysophosphatidic acid, and TGF-β 2 stimulated significant increases in Erk1/2 phosphorylation, paralleled by profound increases in fibronectin, serum response factor (SRF), and α-SMA expression. Treatment of RhoA-activated TM cells with inhibitors of Rho kinase or Erk, on the other hand, decreased fibronectin and α-SMA levels. Although suppression of SRF expression (both endogenous and RhoA, TGF-β 2 -stimulated) via the use of short hairpin RNA decreased α-SMA levels, fibronectin was unaffected. Conversely, fibronectin induced α-SMA expression in an SRF-dependent manner. Collectively, data on RhoA-induced changes in actomyosin contractile activity, ECM synthesis/assembly, and Erk activation, along with fibronectin-induced α-SMA expression in TM cells, reveal a potential molecular interplay between actomyosin cytoskeletal tension and ECM synthesis/assembly. This interaction could be significant for the homeostasis of aqueous humor drainage through the pressure-sensitive trabecular pathway.
    Type of Medium: Online Resource
    ISSN: 0363-6143 , 1522-1563
    URL: Article
    DOI: 10.1152/ajpcell.00317.2009
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2010
    detail.hit.zdb_id: 1477334-X
    SSG: 12
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