June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Effects of bisphosphonates on cytotoxicity and cytokine expression in hRPE cells in vitro
Author Affiliations & Notes
  • Chris Or
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, BC, Canada
  • Jing Cui
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, BC, Canada
  • Joanne Matsubara
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, BC, Canada
  • Farzin Forooghian
    Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, BC, Canada
    Ophthalmology, St Paul's Hospital, Vancouver, BC, Canada
  • Footnotes
    Commercial Relationships Chris Or, None; Jing Cui, None; Joanne Matsubara, None; Farzin Forooghian, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 146. doi:
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      Chris Or, Jing Cui, Joanne Matsubara, Farzin Forooghian; Effects of bisphosphonates on cytotoxicity and cytokine expression in hRPE cells in vitro. Invest. Ophthalmol. Vis. Sci. 2013;54(15):146.

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

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Abstract

Purpose: Bisphosphonates are the most commonly prescribed drugs used to treat osteoporosis. In addition to a recent report supporting an association between bisphosphonate use and ocular inflammation (Etminan et al., 2012), preliminary data also support an association between bisphosphonate use and age-related macular degeneration (AMD). Therefore, we studied the effects of bisphosphonates on primary culture of human retinal pigment epithelium (hRPE), a cell type known to secrete pro-inflammatory cytokines in the outer retina. Alendronate, an amino-bisphosphonate, and etidronate, a non-amino-bisphosphonate, were selected for this experiment as they are members of the two structurally different classes of bisphosphonates.

Methods: Primary cultures of hRPE were serum-starved for 24 hours and then treated for 24 hours with alendronate (0.0001, 0.1, 100 µM) and etidronate (0.01, 1 µM). Cell viability was measured using the MTT assay. Investigation of cytokines induced by bisphosphonates was performed using a human cytokine 29-Plex Panel (Bio-Plex) array and the results were analyzed with an ANOVA.

Results: Etidronate, at the lower concentration, significantly increased the expression of IL-6 (p=0.03) and IL-8 (p=0.04). At the higher concentration, etidronate significantly decreased the expression of GM-CSF (p=0.02) and bFGF (p=0.02). Alendronate, at the highest concentration, significantly increased the expression of IL-8 (p=0.02) and decreased the expression of eotaxin (p=0.02). Alendronate also significantly decreased the expression of bFGF at all concentrations (p<0.05). Alendronate and etidronate did not significantly alter the expression of the other cytokines measured. Cell viability was not significantly affected by either alendronate or etidronate treatment for 24h.

Conclusions: Alendronate and etidronate display dose dependent effects in hRPE cells. Etidronate at lower concentration and alendronate at higher concentration appear to induce pro-inflammatory effects. In addition, anti-angiogenic effects of both drugs were demonstrated by the reduction in bFGF and eotaxin expression observed with the highest concentration of alendronate. The anti-angiogenic effects observed are consistent with a previous study (Nagai et al., 2007). Further studies are required to elucidate the association between bisphosphonate use and AMD.

Keywords: 412 age-related macular degeneration • 557 inflammation • 490 cytokines/chemokines  
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