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Ikram El-Zaoui, Brigitte Goldenberg, lorena Redondo-morata, Simon Scheuring, Alicia Torriglia, Francine Behar Cohen, ; Glucocorticoids induced cataracts trigger AQP0 expression and mechanical heterogeinity of the lens membrane. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2645.
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<br /> Lens cell membranes contain aquaporin-0 (AQP0). AQP0 forms a channel in the membrane that allows the flux of electrolytes and participates cell adhesion, contributing to lens transparency. Treatment with glucocorticoids (GCs) is a well known factor of risk for cataract development.However, the pathogenic mechanisms of these cataracts have not been clearly elucidated. In this work we study if GCs affect AQP0 expression, and if these presumed changes are GCs receptors’ dependent. We further investigate the effect of GCs in the nanomechanical response of the cell lens lipid membrane.
Clear rat lenses were treated ex vivo with Dexamethasone (Dexa, 0.5 and 5 µM) or Triamcinolone Acetonide (TA, 10 µM and 1mg) for 1, 2, 4 and 6 days. Lenses were examined daily for the development of opacities that quantified photographically using an image analysis software. The mRNA and protein level of AQP0, glucocorticoids receptors (GR) and mineralocorticoid receptor (MR) were examined by reverse transcription polymerase chain reaction and Western blot analysis.Native membranes were isolated from fiber cells from rat. Elasticity maps of lens cell lipid extracts in the presence of 460 mM TA, 720 mM Dexa or 2 mM Dexamethasone phosphate (Dexa-Ph) were obtained by the Atomic Force Microscopy (AFM).
The lens opacities increased a in time-dependant and dose-dependent fashion with both GCs. The opacities were more important in TA than in Dexa groups. mRNA expression levels of GR, MR and AQP0 in the epithelium were variable depending on the drug and the doses. Inhibition of GCs receptors using antagonists did not modify significantly theses responses. Mechanical mapping of supported lens cell lipid bilayer extracts revealed rich mechanical heterogeneity. This heterogeneity is higher in the presence of TA. Upon the addition of Dexa-Ph, the lens membrane displays a decrease in the elasticity.
The results suggested that TA is more cataratogenic than Dexa. The studied drugs modify the expression of AQP0 through non-genomic pathways. Elasticity measurements evidenced the mechanical heterogeneity of native lens lipid membranes and that its mechanical stability can be altered upon the addition of GCs. Altogether, this study contributes to a better understanding of the mechanisms of Corticosteroids induced cataracts
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