April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Cyclosporine A Induces Autophagic Cell Death in Lens Epithelial Cells to Prevent Posterior Capsule Opacification Ex Vivo
Author Affiliations & Notes
  • Heather L Chandler
    The Ohio State University, Columbus, OH
  • Rachel B Matusow
    The Ohio State University, Columbus, OH
  • Elizabeth Curto
    The Ohio State University, Columbus, OH
  • Kristen J Gervais
    The Ohio State University, Columbus, OH
  • Footnotes
    Commercial Relationships Heather Chandler, None; Rachel Matusow, None; Elizabeth Curto, None; Kristen Gervais, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3046. doi:https://doi.org/
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      Heather L Chandler, Rachel B Matusow, Elizabeth Curto, Kristen J Gervais; Cyclosporine A Induces Autophagic Cell Death in Lens Epithelial Cells to Prevent Posterior Capsule Opacification Ex Vivo. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3046. doi: https://doi.org/.

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

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Abstract

Purpose: To determine the appropriate Cyclosporine A (CsA) dose and minimum drug delivery time needed to prevent posterior capsule opacification (PCO) in an ex vivo model and evaluate the mechanism of CsA-induced cell death.

Methods: Lens capsules were harvested from canine cadaver eyes using an established ex vivo model of PCO. Lens capsules were treated with 0, 5, or 10 µg/mL CsA for 0, 2, 3, 4, 5, 6, or 7 days, and then maintained in culture for a total of 28 days in the absence of drug. CsA-treated lens epithelial cells (LEC) underwent routine transmission electron microscopy (TEM), western blotting, and fluorescent staining to evaluate the mechanism of cell death.

Results: Lens capsules treated with 5, 6, or 7 days of 10 µg/mL CsA showed a significant decrease in ex vivo PCO formation; 7 days of drug delivery was sufficient to prevent PCO. Morphologically, CsA-treated LEC were swollen, had intact nuclei, lacked peripheral chromatin condensation, and demonstrated prominent vacuolization; TEM revealed autophagosomes. LC3-II protein expression and acridine orange fluorescence increased in CsA-treated cells. Dose dependent changes were observed in all experiments.

Conclusions: Seven days of intracapsular CsA drug delivery prevented ex vivo PCO formation. Morphologic changes and TEM suggest that CsA is able to induce LEC death via autophagy; this is a novel finding in the lens. Acridine orange is a marker for acidic vesicles and LC3-II is a protein involved in mediating autophagic death. Expression of these markers in CsA-treated LEC further supports this new mechanism of drug-induced LEC death.

Keywords: 652 posterior capsular opacification (PCO)  
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