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M. Shivanna, S.S. Jalimarada, Y. Guo, S. Srinivas; Effects of Lovastatin on Actin Cytoskeleton in Corneal Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1618.
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Statins reduce intraocular pressure by increasing the aqueous outflow facility across the trabecular meshwork (TM) (J.Song et al, IOVS, 46, 2424–32, 2005). The present study has investigated the effects of lovastatin on actin cytoskeleton in corneal endothelial cells.
Experiments were carried out in primary culture of bovine corneal endothelial cells. MLC phosphorylation, a biochemical marker of contractility of actin cytoskeleton, was assayed by urea glycerol gel electrophoresis and western blotting. Changes in organization of cortical cytoskeleton were examined by immunocytochemical staining of actin with phalloidin. Flow cytometry was used to assay apoptosis in response to lovastatin.
Exposure to lovastatin (30 µm; 24 hrs) led to significant MLC dephosphorylation (47.2% of control). Co–treatment with lovastain also blocked MLC phosphorylation in response to thrombin (2 U/ml; 20 min). Actin cytoskeleton, which appears as a thick cortical band in untreated cells, was completely disrupted upon treatment with lovastatin. Actin clumping was evident with consequent damage to polygonal morphology of the endothelium. Lovastatin was also found to induce apoptosis (8%).
Despite the potential for statins to be useful as ocular hypotensive drugs, their side effects on corneal endothelium appear to be important. At concentrations found to be effective in lowering IOP, lovastatin induced excessive MLC dephosphorylation (consistent with reduced isoprenylation of RhoA) and cell death. The former can cause cell de–adhesion and induce focal loss of barrier integrity of the corneal endothelium which is essential for corneal transparency.
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