Alterations in human trabecular meshwork cell homeostasis by selenium

Exp Eye Res. 2006 Apr;82(4):637-47. doi: 10.1016/j.exer.2005.08.024. Epub 2005 Nov 10.


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 microM MSeA for 24hr, the majority remained in the conditioned medium. Selenium-induced morphological changes (< or =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 microM) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / analysis
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Eye Proteins / antagonists & inhibitors
  • Homeostasis / physiology*
  • Humans
  • Infant
  • Integrins / physiology
  • MAP Kinase Signaling System / physiology
  • Manganese / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Selenium / analysis
  • Selenium / pharmacokinetics
  • Selenium / pharmacology*
  • Signal Transduction / physiology
  • Time Factors
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / drug effects*
  • Trace Elements / pharmacology
  • Umbilical Veins / cytology
  • Zinc / pharmacology


  • Antioxidants
  • Eye Proteins
  • Integrins
  • Trace Elements
  • Manganese
  • Matrix Metalloproteinase 2
  • Selenium
  • Zinc