June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells
Author Affiliations & Notes
  • Bo Tian
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Ahmad Al Moujahed
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Boston University School of Medicine, Boston, Massachusetts, United States
  • Peggy Bouzika
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Yijun Hu
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Shoji Notomi
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Pavlina Tsoka
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Joan W Miller
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Haijiang Lin
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Department of Ophthalmology & Visual Sciences, University of Massachusetts Medical School , Worcester, Massachusetts, United States
  • Demetrios G. Vavvas
    Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Harvard Medical school, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Bo Tian, None; Ahmad Al Moujahed, None; Peggy Bouzika, None; Yijun Hu, None; Shoji Notomi, None; Pavlina Tsoka, None; Joan Miller, Alcon (C), Amgen, Inc. (C), KalVista Pharmaceuticals Ltd. (C), Maculogix, Inc. (C), ONL Therapeutics, LLC (P), Valeant Pharmaceuticals (P); Haijiang Lin, None; Demetrios Vavvas, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2279. doi:
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      Bo Tian, Ahmad Al Moujahed, Peggy Bouzika, Yijun Hu, Shoji Notomi, Pavlina Tsoka, Joan W Miller, Haijiang Lin, Demetrios G. Vavvas; Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2279.

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

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Abstract

Purpose : RPE dysfunction plays an essential role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of irreversible blindness in the elderly of developed countries. High dose atorvastatin was reported to result in visual improvement in a subset of high-risk subgroup of AMD patients in our previous pilot Phase1/2 clinical study. However, its effect on RPE cells has not been fully elucidated. The purpose of this study is to explore the effect of high dose atorvastatin on phagocytic function of ARPE-19 cells as well as the secretion of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD.

Methods : ARPE-19 cells were incubated with polystyrene microspheres along with different doses of atorvastatin. The percentage of phagocytic ARPE-19 cells and the mean fluorescence intensity (MIF) of engulfed particles were measured after 6 hours by flow cytometry. Furthermore, the effect of atorvastatin on cell membrane fluidity was assessed by Fluorescence Recovery After Photo-bleaching (FRAP) measurements. ARPE-19 cells were then pretreated by atorvastatin and then challenged with cholesterol crystals for 6 hours, or oxidized low-density lipoproteins (ox-LDL) for 18 hours. The phagocytic function was determined using the same method as above. Subsequently, the cells were treated with different doses of atorvastatin for 16 hours after being primed with IL-1α, and then incubated with cholesterol crystals or ox-LDL. Τhe levels of IL-6 and IL-8 were evaluated using western blot or ELISA after 6 hours incubation.

Results : Atorvastatin treatment promoted phagocytic function of ARPE-19 cells by increasing the percentage of phagocytic cells and the MIF of engulfed particles compared to the control group in a dose-dependent manner (p<0.05). Interestingly, atorvastatin also increased the ARPE-19 cell membrane fluidity compared to the control (p<0.05). In addition, pre-treatment with atorvastatin abrogated the decreased percentage of phagocytic cells and the MIF, as well as the IL-6 and IL-8 secretion induced by cholesterol crystals and ox-LDL (p<0.05).

Conclusions : Our study shows that hydrophobic statins, at high dose enhance and preserve the phagocytic function of RPE in cell culture while also exhibiting anti-inflammatory properties. More investigation is needed on the role of statins in conditions such as AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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