December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
Glucocorticoid-Induced Changes in Lens Epithelial Cells
Author Affiliations & Notes
  • ER James
    Ophthalmology Med Univ of South Carolina Charleston SC
  • JC Goldstein
    Cellular Immunology La Jolla Institute for Allergy and Immunology San Diego CA
  • Footnotes
    Commercial Relationships   E.R. James, None; J.C. Goldstein, None. Grant Identification: EY013786
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2376. doi:
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      ER James, JC Goldstein; Glucocorticoid-Induced Changes in Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2376.

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

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Abstract: : Purpose: Cataracts are a consequence of steroid therapy. Studies aimed at elucidating the mechanism of steroid-induced cataract have focused principally on the binding of steroids to lens crystallins, steroid-mediated crystallin cross-linking and oxidation. However, data from these studies have not identified a causal mechanism. Only those steroids with glucocorticoid (GC) activity appear to cause steroid cataracts which suggests the glucocorticoid receptor (GR) may be involved. There is evidence both for and against the existence of GR in the lens. The purpose of this study was to determine the effects of GC on lens epithelial cells in vitro and to investigate the mechanisms underlying these changes, with the goal of understanding the process of induction of steroid cataract. Methods: Sub-confluent rabbit lens epithelial cells (LEC) (N/N1003A, kindly donated by Dr. John Reddan) were exposed to GC or GC antagonists and assayed for viability using Alamar Blue and for glutathione (GSH) content and caspase activity. Human lens sections were probed with antibodies to GR and viewed by confocal microscopy. Primers specific for the rabbit gamma-glutamyl cysteine synthase (GCS) cDNA were used in RT-PCR to monitor changes in GCS expression following dexamethasone (Dex) administration. Results: FITC-Dex demonstrated punctate cytoplasmic localization at 1 and 24 hr but no nuclear translocation was apparent. The existence of GR in lens sections was not obvious with the antibodies used. GSH was reduced by 30% within 3 hr of Dex treatment, however, there was no discernable change in GCS mRNA levels. Exposure to Dex or to TNFalpha produced no change in viability up to 24 hr, yet addition of both compounds together reduced cell viability by 60%. Caspase-3 activity increased by 15 fold 24 hr after Dex addition. Conclusion: The data are equivocal for involvement of GR in induction of steroid cataract. The data suggest GC potentially induce oxidant stress in LEC. Additionally, either one or both of the main apoptotic pathways may be triggered by steroid treatment. By 24 hr Dex treatment had induced elevated caspase-3 activity but this had not resulted in cell death, cell shrinkage or chromatin condensation possibly indicating at least partial attenuation of the apoptotic process.

Keywords: 338 cataract • 323 apoptosis/cell death • 377 corticosteroids 

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