July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Characterization of RPE Cell Death Induced by 4-HNE
Author Affiliations & Notes
  • Yao Tong
    Department of cell and molecular biology, Tulane University, New Orleans, Louisiana, United States
  • Bo Yu
    Department of cell and molecular biology, Tulane University, New Orleans, Louisiana, United States
  • jing ma
    Department of cell and molecular biology, Tulane University, New Orleans, Louisiana, United States
  • Shusheng Wang
    Department of cell and molecular biology, Tulane University, New Orleans, Louisiana, United States
    Department of Ophthalmology, Tulane University, Louisiana, United States
  • Footnotes
    Commercial Relationships   Yao Tong, None; Bo Yu, None; jing ma, None; Shusheng Wang, None
  • Footnotes
    Support  NIH grants EY021862, EY026069
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1683. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yao Tong, Bo Yu, jing ma, Shusheng Wang; Characterization of RPE Cell Death Induced by 4-HNE. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1683.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Degeneration of the retinal pigment epithelial (RPE) underscores the pathology in geographic atrophy (GA), a late stage dry age-related macular degeneration (AMD). Oxidative stress and aging are known to contribute to GA pathogenesis. However, how RPE cells die in GA is still controversial. 4-Hydroxynonenal (4-HNE) is an oxidative stress marker produced by lipid peroxidation, which is accumulated in aging cells and could be related to age-related diseases. The goal of the study is to determine the mechanism of 4-HNE-induced RPE cell death.

Methods : ARPE-19 cells were treated with 4-HNE at different concentrations to induce cell death. Inhibitors of apoptosis, necroptosis, pyroptosis and ferroptosis pathways, were used to test for their effect on cell viability. Cell morphology and molecular markers (including PYCARD and RIPK3) were examined under a microscope. ATP and ROS levels were measured using standard methods.

Results : We found that 4-HNE (5-10 ug/ml) induces significant RPE cell death, consistent with significantly decreased cellular ATP but increased ROS levels. Necrosis inhibitor Necrostatin-7 and ferroptosis inhibitors liproxstatin-1 and DFO, but not apoptosis inhibitors, prevented 4-HNE-induced RPE cell death. On the molecular level, both inflammasome and necrosome are activated in RPE cells treated with 4-HNE, as shown by PYCARD and RIPK3 visualization.

Conclusions : Ferroptosis and/or necroptosis, but not apoptosis, underlie RPE death induced by 4-HNE. Crosstalk between different cell death pathways may occur when RPE cells are under oxidative stress. The inhibitors from our study may have therapeutic implications for GA.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×