May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Selenium Effects on Integrin Activity and Intracellular Signaling in Trabecular Meshwork Cells.
Author Affiliations & Notes
  • S.M. Conley
    Ophthalmology, The University of Arizona, Tucson, AZ
  • B.S. McKay
    Ophthalmology, The University of Arizona, Tucson, AZ
  • W.D. Stamer
    Ophthalmology, The University of Arizona, Tucson, AZ
  • Footnotes
    Commercial Relationships  S.M. Conley, None; B.S. McKay, None; W.D. Stamer, None.
  • Footnotes
    Support  EY15115, Research to Prevent Blindness, Mr. and Mrs. Polak
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4416. doi:
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    • Get Citation

      S.M. Conley, B.S. McKay, W.D. Stamer; Selenium Effects on Integrin Activity and Intracellular Signaling in Trabecular Meshwork Cells. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4416.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The Nutritional Prevention of Cancer intervention trial has shown an increased incidence of glaucoma in selenium–supplemented individuals. Previously, our group has shown that selenium inhibits the secretion of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in human trabecular meshwork (TM) cells, a likely site of pathology in primary open–angle glaucoma. The purpose of the present study is to investigate intra– and extracellular mechanisms responsible for selenium mediated effects. Methods:Confluent TM cultures (human or porcine) were treated with methylseleninic acid (MSeA) in serum–free medium at sequential time points. Changes in cellular morphology were documented by phase–contrast microscopy, while protease secretion and phosphorylation status of mitogen–activating protein kinase (MAPK) were followed by SDS–PAGE/western blotting. To investigate MSeA interaction with TM integrins, effects of manganese (a divalent cation that activates integrins) on morphology of TM cultures were recorded both in the presence and absence of MSeA. Results: Morphological changes in TM cells consistent with integrin inactivation were observed in a dose– and time–dependent manner after treatment with MSeA. Changes in morphology were seen at doses as low as 1µM MSeA, and as soon as 1–3 hours after 10µM MSeA treatment. MAPK phosphorylation was noticeably decreased 3–6 hours after 10µM selenium treatment, a change that persisted as long as 24hrs. Decreased secretion of MMP–2 also appeared 3–6 hours after selenium treatment. In porcine trabecular meshwork cells, the morphological changes associated with 15µM and 30µM MSeA were blocked by co–administration of 500µM manganese. Conclusions: Results suggest a role for integrin adhesion receptors and MAPK signaling in the effect of selenium on TM cells. Combined effects on integrin receptors and protease secretion may be one way selenium can impair aqueous outflow and lead to the development of glaucoma

Keywords: enzymes/enzyme inhibitors • extracellular matrix • trabecular meshwork 
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