Purchase this article with an account.
S.M. Conley, W.D. Stamer; Selenium Toxicity in Trabecular Meshwork Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1348.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The Nutritional Prevention of Cancer intervention trial has shown an increased incidence of glaucoma in selenium–supplemented individuals. Previously, we have shown that selenium inhibits the secretion of matrix metalloproteinases from, and causes gross morphological changes in human trabecular meshwork (HTM) cells, a likely contributor in the pathology of primary open–angle glaucoma. The purpose of the present study was to investigate cellular mechanisms responsible for selenium–induced physiological effects. Methods: Confluent HTM cells were treated with methylseleninic acid (selenium), exposed to radiolabeled methionine/cysteine, and protein synthesis plus protein secretion were monitored over time. Effects of selenium on total cellular ATP were assessed via a bioluminescent luciferase assay. Using mass spectrometry, selenium uptake into cultured cells was quantified. All experiments used human umbilical vein endothelial cells as controls. Results: Physiologically relevant (1µM) doses of selenium significantly inhibited total cellular protein synthesis (45% less than control, p<0.01), but did not affect total protein secretion. Significant decreases in protein secretion were noted in a dose–dependent manner at higher doses (5–10µM). Total cellular ATP also decreased as selenium concentration increased (5–50µM). Conclusions: Results show that selenium, at physiologically relevant concentrations disrupts cell machinery. In HTM cells, interruption of normal homeostasis by selenium may lead to functional impairment that ultimately affects conventional outflow facility.
This PDF is available to Subscribers Only