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Research Paper|Volume 12, Issue 17|pp 17367—17379

G-protein coupled estrogen receptor activation protects the viability of hyperoxia-treated primary murine retinal microglia by reducing ER stress

Rong Li1, Yao Wang2, Pei Chen2, Jiamin Meng3, Hongbing Zhang2
  • 1Department of Ophthalmology, The First Affiliated Hospital of Xi'an Medical University, Xi’an 710077, Shaanxi, PR China
  • 2Department of Ophthalmology, Eye Institute of Shaanxi Province and Xi'an First Hospital, Xi'an 710002, Shaanxi, PR China
  • 3School of Life Sciences, Northwest University, Xi’an 710069, Shaanxi, PR China
Received: February 25, 2020Accepted: June 19, 2020Published: September 13, 2020
https://doi.org/10.18632/aging.103733

Copyright: © 2020 Li 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

In this study, we investigated the effects of G-protein coupled estrogen receptor (GPER) activation in the early phase of retinopathy of prematurity (ROP) and its association with endoplasmic reticulum (ER) stress using primary murine retinal microglia as an experimental model. Fluorescence microscopy results show that the CD11c-positive primary retinal microglia in vitro cultured for 14 days were GPER-positive. GPER activation using GPER-agonist G-1 reduced autophagy and increased the viability of the hyperoxia-treated primary murine retinal microglia. Furthermore, GPER activation reduced the expression of ER stress-related proteins, IRE1α, PERK and ATF6 in the hyperoxia-treated primary murine retinal microglia compared to the corresponding controls. GPER activation significantly reduced a time-dependent increase in IP3R-dependent calcium release from the ER, thereby maintaining higher calcium levels in the ER of hyperoxia-treated primary retinal microglia. However, the protective effects of G-1 on the hyperoxia-treated primary retinal microglia were eliminated by inactivation of GPER using the GPER-antagonist, G-15. In conclusion, our study demonstrates that GPER activation enhances the survival of hyperoxia-treated primary retinal microglia by reducing ER stress. Our study demonstrates the therapeutic potential of GPER agonists such as G-1 in the early phase of ROP.