Alterations in human trabecular meshwork cell homeostasis by selenium

Shannon M. Conley, Brian S Mckay, A Jay Gandolfi, W. Daniel Stamer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Epidemiological evidence indicates that selenium supplementation may increase risk for glaucoma and ocular hypertension. The purpose of this study was to determine the effects of selenium on trabecular meshwork cells, a likely site of pathology for glaucoma. Human trabecular meshwork (HTM) cells and human umbilical vein endothelial cells (HUVECs) were treated with selenium (MSeA) at or near physiologically relevant concentrations. Selenium uptake by cells was monitored using mass spectrometry. Alterations in protein secretion, intracellular signaling, and cell morphology were monitored; and the role of integrin signaling in MSeA-induced morphological alterations was investigated using divalent cation treatments. Radiolabeling was used to assess protein synthesis and secretion, while luciferase and MTT assays monitored total cellular ATP and cell viability, respectively. Whereas detectible changes in intracellular selenium were observed after exposure to 1-10 μM MSeA for 24 hr, the majority remained in the conditioned medium. Selenium-induced morphological changes (≤3 hr) occurred before alterations in protein secretion and intracellular signaling (3-6 hr). Zinc treatment prevented selenium-mediated alterations in protein secretion and changes in cell-matrix adhesion. MSeA treatment (5 μM) led to a 60% decrease in protein synthesis after 3 hr and a 30% reduction in secretion, although significant alterations in cell viability and total ATP were not observed after MSeA treatment. Selenium altered several indicators of HTM cell homeostasis, but did not affect viability at physiologically relevant doses. Similar results with HUVECs have implications for understanding selenium's mechanisms of action as an anti-angiogenic agent.

Original languageEnglish (US)
Pages (from-to)637-647
Number of pages11
JournalExperimental Eye Research
Volume82
Issue number4
DOIs
StatePublished - Apr 2006

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Trabecular Meshwork
Selenium
Homeostasis
Intracellular Signaling Peptides and Proteins
Human Umbilical Vein Endothelial Cells
Glaucoma
Cell Survival
Adenosine Triphosphate
Cell-Matrix Junctions
Ocular Hypertension
Proteins
Divalent Cations
Conditioned Culture Medium
Luciferases
Integrins
Zinc
Mass Spectrometry
Pathology

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Alterations in human trabecular meshwork cell homeostasis by selenium. / Conley, Shannon M.; Mckay, Brian S; Gandolfi, A Jay; Daniel Stamer, W.

In: Experimental Eye Research, Vol. 82, No. 4, 04.2006, p. 637-647.

Research output: Contribution to journalArticle

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