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 Long^1,^2,⁵, Mengshan He^3,⁷, Weiming Yan⁴, Wei Chen¹, Dongyu Wei^5,⁶, Siwang Wang³, Zuoming Zhang^5,⁶, Wei Ge¹, Tao Chen^5,⁶

¹Department of General Practice, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
²Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
³Department of Chinese Material Medical and Natural Medicines, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
⁴Department 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
⁵Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
⁶Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
⁷Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China

* Equal contribution

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

https://doi.org/10.18632/aging.202325

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.

Abstract

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 (UPR^ER) 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 UPR^ER during the aging process to improve retinal function and structure.