Abstract：
PURPOSE:To investigate the potential protective effect of novel G protein coupled estrogen receptor (GPER1) against the neurotoxicity induced by NMDA in the mouse retina. METHODS:We induce retinal ganglion cells (RGCs) toxic injury through intravitreal injection of NMDA or acute ocular hypertension (AOH) induced by anterior chamber infusion with saline. Endogenous ligand 17-β-estradiol (E2), GPER1 agonist (G-1), and E2 with GPER1 antagonist (G-15) or classic estrogen receptor α and β (ERα and ERβ) antagonist tamoxifen (TAM) were subcutaneous administered before NMDA to identify the possible involved receptors. Immunofluorescence staining was performed to explore the survival of RGCs and Müller cell gliosis. TUNEL staining was used to evaluate the RGC apoptosis. The involved molecular pathway was detected via antibody array expression profiling. RESULTS:Activation of estrogen receptor by E2 or G-1 could significantly rescue the RGCs injury in NMDA administration. The protective effect was carried exclusively by GPER1 activation. E2 application can still mimicked the protective function when estrogen receptor α and β (ERα and ERβ) blocked by tamoxifen (TAM), while the effects was blocked by GPER1 antagonist G-15. Moreover, the TUNEL positive RGCs and GFAP expression level were both attenuated in G-1 application and the effects could be reversed by G-15. In addition, application of the PI3K/Akt antagonist LY294002 counteracted the effect of G-1. And a number of apoptosis regulatory factors decreased dramatically in the G-1 group, including Bad, Caspase 3, Caspase 7, Smad2, P-53 and TAK1. Also, similar protective effect of G-1 was spotted in acute ocular hypertension (AOH) model. CONCLUSION:Estrogen played a protective role via a novel estrogen receptor, GPER1, instead of classical receptors ERα or ERβ. Activation of GPER1 attenuated RGCs apoptosis and Müller cells gliosis, indicating GPER1 as a potential treatment target in RGCs degeneration diseases.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Jiang M,Ma X,Zhao Q,Li Y,Xing Y,Deng Q,Shen Ydoi
10.1016/j.exer.2019.107826subject
Has Abstractpub_date
2019-12-01 00:00:00pages
107826eissn
0014-4835issn
1096-0007pii
S0014-4835(19)30504-4journal_volume
189pub_type
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