Research Paper Volume 12, Issue 16 pp 16579—16596

Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury

Jing-Yao Song1, , Bin Fan1, , Lin Che1, , Yi-Ran Pan1, , Si-Ming Zhang1, , Ying Wang2, , Victoria Bunik3, , Guang-Yu Li1, ,

  • 1 Department of Ophthalmology, Second Hospital of Jilin University, Changchun, China
  • 2 Department of Hemooncolog, Second Hospital of Jilin University, Changchun, China
  • 3 A.N.Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia

Received: February 11, 2020       Accepted: June 30, 2020       Published: August 28, 2020
How to Cite

Copyright © 2020 Song et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 cells). Suppressing either oxidative stress or ER stress was protective against light damage in 661W and ARPE-19 cells and N-acetyl-L-cysteine treatment markedly inhibited the activation of ER stress caused by light exposure. Moreover, suppressing autophagy with 3-methyladenine significantly attenuated light-induced cell death. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.


SAL: Salubrinal; 3MA: 3-methyladenine; NAC: N-acetyl-L-cysteine; HCO: Hydroxychloroquine; ROS: reactive oxygen species; GSH: glutathione; GSSG: oxidized glutathione; PDI: resident protein disulfide isomerases; ERO1: endoplasmic reticulum oxidoreduction 1; UPR: unfolded-protein response; ER: endoplasmic reticulum; ATF6: activating transcription factor 6; IRE1: inositol-requiring enzyme 1; XBP1: X-box binding protein; EIF2: eukaryotic translation initiation factor 2; ATF4: activating transcription factor 4; CHOP: C/EBP homologous protein; AMD: age-related macular degeneration; Lt: Light exposure.