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Qinqin Deng, Yiqiao Xing, Mengnan Jiang, Xueyun Ma, Qingqing Zhao, Wei Lu, Xinlan Lei, Ying Li, Yin Shen; A novel estrogen receptor GPER1 activation promote retinal ganglion cell survivor in normal tension glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4855. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
G protein coupled estrogen receptor (GPER1) is a novel estrogen receptor (ER) located in the plasma membrane. The expression and functions of GPER1 in retina was largely unknown. In this project, we performed NMDA model to identity the potential functions of GPER1 in mouse retina.
Intravitreal injection of NMDA was performed to induce retinal ganglion cells (RGCs) damage. Subcutaneous administered of E2, GPER1 agonist (G-1) or antagonist (G-15) once a day for 14 days before NMDA injection. Immunofluorescence staining was performed to explore the survivor of RGCs and Müller cell gliosis. TUNEL staining was used to study the apoptosis. The molecular mechanism were detected via antibody microarray analysis.
We firstly identified the expression of GPER1 in mouse retina, which mainly located in the ganglion cells layer (GCL) and inner nuclear layer (INL). Application of E2 or G-1 significantly increased the survivor of RGCs. E2+tamoxifen (TAM), estrogen receptor α and β (ERα and ERβ) antagonist, mimic the same protective effects, whereas E2+G-15 did not. Meanwhile, the TUNEL positive RGCs and GFAP expression were attenuated in E2 and G-1 groups. Application of the PI3K/Akt antagonist Ly294002 abolished the regulation of G-1. And the antibody microarray indicated the apoptosis modulators reducing: Bad, Caspase 3, Caspase 7, Smad2, P-53 and TAK1 in G-1 group. The similar modulation of G-1 was found in acute ocular hypertension (AOH) model.
Estrogen exhibited protective effects in mouse retina, which was modulated via novel estrogen receptor GPER1, but not classical receptors ERα and ERβ, indicating a potential therapy target of GPER1 in retina diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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