April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Simvastatin Affects Viability, Morphology and Phagocytosis of Human Cells in Culture
Author Affiliations & Notes
  • R. Sui
    NEI/NIH, Bethesda, Maryland
    Ophthalmology, Peking Union Medical College Hospital, Beijing, China
  • N. Gordiyenko
    NEI/NIH, Bethesda, Maryland
  • N. Strunnikova
    NEI/NIH, Bethesda, Maryland
  • C. Zhi
    NEI/NIH, Bethesda, Maryland
  • I. MacDonald
    NEI/NIH, Bethesda, Maryland
    Ophthalmology, University of Alberta, Edmonton, Alberta, Canada
  • Footnotes
    Commercial Relationships  R. Sui, None; N. Gordiyenko, None; N. Strunnikova, None; C. Zhi, None; I. MacDonald, None.
  • Footnotes
    Support  NIH Intramural
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3406. doi:
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      R. Sui, N. Gordiyenko, N. Strunnikova, C. Zhi, I. MacDonald; Simvastatin Affects Viability, Morphology and Phagocytosis of Human Cells in Culture. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3406.

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

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Methods: : Dermal fibroblasts were cultured from CHM patients and age-matched controls. Human fetal RPE cells were transfected with non-targeting and Rep1 siRNA. Cell proliferation and viability were evaluated by mitochondrial dehydrogenase activity. Morphological changes were examined by phase-contrast microscopy. Actin reorganization was observed by immunocytochemistry and confocal microscopy. Phagocytosis was induced in human fetal RPE cells with bovine photoreceptor outer segments (POS) and quantified. The prenylation of small G-proteins was assessed comparing their distribution between cell membrane fractions (prenylated) and cytosolic fractions (unprenylated).

Results: : Fibroblasts and hfRPE cells treated with statin showed decreased proliferation in a dose- and time-dependent pattern. Phagocytosis of POS was reduced when hfRPE cells were incubated with simvastatin. Phagocytosis by hfRPE cells after Rep1 knock down was significantly reduced by simvastatin. Similarly, simvastatin induced actin rearrangement and reduced cell viability more dramatically in. CHM fibroblasts (lacking Rep-1) and hfRPE cells after Rep1 knock down. Less Rab and Rac proteins were expressed in cytosolic fractions after treatment with simvastatin.

Conclusions: : Statin inhibited cell proliferation, disrupted the cytoskeleton, and decreased hfRPE phagocytosis. These effects were independent of cholesterol reduction but due to insufficient isoprenylation of small G-proteins. Alternates to statin therapy could be considered for CHM patients with pre-existing deficient isoprenylation.

Keywords: phagocytosis and killing • signal transduction • cell survival 

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