Research Paper Volume 13, Issue 2 pp 2750—2767

ALDH2 protects naturally aged mouse retina via inhibiting oxidative stress-related apoptosis and enhancing unfolded protein response in endoplasmic reticulum

Pan Long1,2,5, *, , Mengshan He3,7, *, , Weiming Yan4, *, , Wei Chen1, , Dongyu Wei5,6, , Siwang Wang3, , Zuoming Zhang5,6, , Wei Ge1, , Tao Chen5,6, ,

  • 1 Department of General Practice, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
  • 2 Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
  • 3 Department of Chinese Material Medical and Natural Medicines, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
  • 4 Department of Ophthalmology, The 900th Hospital of Joint Logistic Support Force, PLA (Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University), Fuzhou 350025, Fujian Province, China
  • 5 Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
  • 6 Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
  • 7 Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
* Equal contribution

Received: January 9, 2020       Accepted: October 1, 2020       Published: December 19, 2020
How to Cite

Copyright: © 2020 Long 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.


During the process of aging, the retina exhibits chronic oxidative stress (OS) damage. Our preliminary experiment showed that acetaldehyde dehydrogenase 2 (ALDH2) could alleviate retinal damage caused by OS. This study aimed to explore whether ALDH2 could inhibit mice retinal cell apoptosis and enhance the function of unfolded protein response in endoplasmic reticulum (UPRER) through reducing OS in aging process. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice. Levels of ALDH2, endoplasmic reticulum stress (ERS), apoptosis and inflammatory cytokines were evaluated. Higher expression of ALDH2 was observed at the outer nuclear layer (ONL) and the inner nuclear layer (INL) in aged ALDH2+ overexpression and aged Alda1-treated mice. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 (GRP78) and ERS-related protein phosphorylated eukaryotic initiation factor 2 (peIF2α) and decreased expression of apoptosis-related protein, including C/EBP homologous protein (CHOP), caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice. The expression of ALDH2 in the retina was decreased in aging process. ALDH2 could reduce retinal oxidative stress and apoptosis, strengthen UPRER during the aging process to improve retinal function and structure.


AD: Alzheimer's disease; AGEs: advanced glycation end products; ALDH2: acetaldehyde dehydrogenase2; ARVO: Association for Research in Vision and Ophthalmology; ATF6: activating transcription factor 6; BiP: immunoglobulin heavy chain binding protein; CHOP: C/EBP homologous protein; DR: diabetic retinopathy; ERG: electroretinography; ERS: endoplasmic reticulum stress; FFA: fluorescence fundus angiography; GRP78: glucose-regulated protein 78; INL: inner nuclear layer; IPL: inner plexiform layer; IRE1: inositol requiring element-1; IS/OS: inner segment/outer segment; ISEVE: International Standards for Visual Electrophysiology; OCT: optical coherence tomography; ONL: outer nuclear layer; OPL: outer plexiform layer; OPs: oscillatory potentials; OS: oxidative stress; PD: Parkinson's disease; PERK: protein kinase R-like endoplasmic reticulum kinase; RNFL: retinal nerve fibre layer; RP: retinitis pigmentosa; RPE: retinal pigment epithelium; UPRER: unfolded protein response in the endoplasmic reticulum.