1. Academic Validation
  2. Photoactivation of N-retinylidene-N-retinylethanolamine compromises autophagy in retinal pigmented epithelial cells

Photoactivation of N-retinylidene-N-retinylethanolamine compromises autophagy in retinal pigmented epithelial cells

  • Food Chem Toxicol. 2019 Sep;131:110555. doi: 10.1016/j.fct.2019.06.002.
Seo Yeon Jeong 1 XiuHui Gu 1 Kwang Won Jeong 2
Affiliations

Affiliations

  • 1 Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, Republic of Korea.
  • 2 Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, Republic of Korea. Electronic address: kwjeong@gachon.ac.kr.
Abstract

As a part of the aging process, N-retinylidene-N-retinylethanolamine (A2E) accumulates in the retina to activate Autophagy in retinal pigmented epithelial cells. However, the effect of A2E photoactivation on Autophagy, which is more clinically relevant, still remains unclear. Here, we investigated the effect of blue LIGHT (BL)-activated A2E on Autophagy in human retinal pigmented epithelial cells, ARPE-19. A significant increase in LC3-II protein was observed when BL was irradiated on ARPE-19 cells containing A2E. The mammalian target of rapamycin (mTOR) pathway was examined to verify whether Autophagy was activated, but no change in Akt, mTOR, and 4EBP phosphorylation was observed. Transcription factor EB (TFEB) target gene expression, which is another pathway involved in Autophagy, was also not altered by A2E and BL. However, intracellular p62 protein levels were significantly increased, which represented the inhibition of autophagic flux. To investigate the mechanism of the suppressed autophagic flux, the lysosomal state was observed. After BL irradiation, lysosomal damage was induced in A2E-treated ARPE-19 cells, and this phenomenon was prevented by treatment with the antioxidant, N-acetylcysteine. Our results suggest that A2E photoactivation compromises Autophagy in ARPE-19 cells and that Reactive Oxygen Species (ROS) play an important role in this process.

Keywords

A2E; ARPE-19; Autophagy; Blue light; Lysosome; ROS.

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