June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Sulforaphane promotes ER stress, autophagy and cell death: implications for posterior capsule opacification
Author Affiliations & Notes
  • Michael Wormstone
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
  • Hanruo Liu
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, China
  • Andrew J O Smith
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
  • Simon Ball
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
  • Yongping Bao
    Norwich Medical School, University of East Anglia, Norwich, United Kingdom
  • Richard Bowater
    School of Biological Sciences, University of East Anglia, Norwich, United Kingdom
  • Ningli Wang
    Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing, China
  • Footnotes
    Commercial Relationships   Michael Wormstone, None; Hanruo Liu, None; Andrew Smith, None; Simon Ball, None; Yongping Bao, None; Richard Bowater, None; Ningli Wang, None
  • Footnotes
    Support  The Humane Research Trust (UK);The Beijing New Star of Science and Technology Fund (H020821380190), Fund of Work Committee for Women and Children of China State Department (2014108), The National Natural Science Fund Projects of China (30471861)and Beijing Scholars of Beijing Municipal Government.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3790. doi:
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    • Get Citation

      Michael Wormstone, Hanruo Liu, Andrew J O Smith, Simon Ball, Yongping Bao, Richard Bowater, Ningli Wang; Sulforaphane promotes ER stress, autophagy and cell death: implications for posterior capsule opacification
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3790.

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

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Abstract

Purpose : Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyantae, sulforaphane (SFN) is reported to exert cytoprotective and cytotoxic actions and the latter may be exploited to treat/prevent PCO.

Methods : The human lens epithelial cell line FHL124 and human lens capsular bag system were used as experimental models. The MTS assay was used to assess cell populations and the LDH assay was employed to assess cell damage/death. To determine migration, a scratch assay was performed. Gene expression and protein levels were determined using real-time PCR and western blot methods respectively. To investigate protein distribution and cell architecture immunofluorescence and transmission electron microscopy were utilized. Level of reactive oxidant species (ROS) was determined using a commercially available kit (Promega). In vitro capsular bags were generated from human donor eyes by simulated cataract surgery, isolated by cutting of the zonules and secured to a 35mm tissue culture dish using entomological pins. Ongoing observations were made using phase-contrast microscopy.

Results : SFN concentrations of 10µM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of ER stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased LC3-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling and inhibition of ERK activation, using U0126, prevented SFN induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of ROS.

Conclusions : Taken together, our findings suggest that SFN is capable of inducing ER stress and autophagy, which could contribute to reduced lens cell growth and viability. SFN could thus serve as a putative therapeutic agent for PCO.

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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