Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery

J Mol Med (Berl). 2017 May;95(5):553-564. doi: 10.1007/s00109-016-1502-4. Epub 2017 Jan 12.

Abstract

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 isothiocyanate, sulforaphane (SFN), is reported to exert cytoprotective and cytotoxic actions, and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10 μM 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 endoplasmic reticulum (ER) stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased microtubule-associated protein 1A/1B-light chain 3 (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 reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO.

Key message: SFN reduces lens epithelial cell growth, migration, and viability. SFN can promote ER stress and autophagy in lens cells. SFN promotes MAPK signaling, and inhibition of MEK can suppress SFN-induced autophagy. ER stress and autophagy in lens cells are likely promoted by ROS production. SFN may help prevent posterior capsule opacification after cataract surgery.

Keywords: Autophagy flux; ER stress; Lens; Posterior capsule opacification; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects*
  • Capsule Opacification / prevention & control
  • Cataract / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Endoplasmic Reticulum Stress / drug effects*
  • Humans
  • Isothiocyanates / pharmacology*
  • Isothiocyanates / therapeutic use
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / metabolism
  • Posterior Capsule of the Lens / drug effects
  • Posterior Capsule of the Lens / metabolism
  • Postoperative Complications / prevention & control
  • Reactive Oxygen Species / metabolism

Substances

  • Isothiocyanates
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • sulforafan