Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells

Sci Rep. 2017 May 24;7(1):2329. doi: 10.1038/s41598-017-02407-7.

Abstract

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin / pharmacology*
  • Cell Line
  • Cholesterol / metabolism*
  • Epithelial Cells
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipoproteins, LDL / metabolism
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Phagocytosis / drug effects
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology

Substances

  • Interleukin-6
  • Interleukin-8
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Cholesterol
  • Atorvastatin