Zinc Protects Oxidative Stress-Induced RPE Death by Reducing Mitochondrial Damage and Preventing Lysosome Rupture

Dinusha Rajapakse, Timothy Curtis, Mei Chen, Heping Xu*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)
175 Downloads (Pure)

Abstract

Zinc deficiency is known to increase the risk of the development of age-related macular degeneration (AMD), although the underlying mechanism remains poorly defined. In this study, we investigated the effect of zinc on retinal pigment epithelium (RPE) survival and function under oxidative conditions. Zinc level was 5.4 μM in normal culture conditions (DMEM/F12 with 10% FCS) and 1.5 μM in serum-free medium (DMEM/F12). Under serum-free culture conditions, the treatment of RPE cells with oxidized photoreceptor outer segment (oxPOS) significantly increased intracellular ROS production, reduced ATP production, and promoted RPE death compared to oxPOS-treated RPE under normal culture condition. Serum deprivation also reduced RPE phagocytosis of oxPOS and exacerbated oxidative insult-induced cathepsin B release from lysosome, an indicator of lysosome rupture. The addition of zinc in the serum-free culture system dose dependently reduced ROS production, recovered ATP production, and reduced oxidative stress- (oxPOS- or 4-HNE) induced cell death. Zinc supplementation also reduced oxidative stress-mediated cathepsin B release in RPE cells. Our results suggest that zinc deficiency sensitizes RPE cells to oxidative damage, and zinc supplementation protects RPE cells from oxidative stress-induced death by improving mitochondrial function and preventing lysosome rupture.
Original languageEnglish
Article number 6926485
Pages (from-to)1-12
JournalOxidative Medicine and Cellular Longevity
Volume2017
DOIs
Publication statusPublished - 14 Nov 2017

Keywords

  • Aging
  • retinal pigment epithelium
  • Zinc
  • oxidative stress
  • Mitochondria
  • lysosome

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

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