GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice

Xuan WANG; Jian YE; Wei LIU

doi:10.16016/j.2097-0927.202312090

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GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice

Basic Medicine | 更新时间：2026-01-09

- GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice
- Journal of Army Medical University Vol. 46, Issue 12, Pages: 1369-1377(2024)
- 作者机构：
  
  400042 重庆，陆军特色医学中心眼科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82171054);the Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0164)
- DOI：10.16016/j.2097-0927.202312090
  CLC： R364.33;R774.1;R977.6
- Received：16 December 2023，
  
  Revised：2024-01-27，
  
  Published：30 June 2024
- 稿件说明：
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Xuan WANG, Jian YE, Wei LIU. GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice[J]. Journal of Army Medical University, 2024, 46(12): 1369-1377.
DOI：

Xuan WANG, Jian YE, Wei LIU. GPER-mediated inhibition of astrocyte activation mitigates retinal neovascularization in oxygen-induced retinopathy mice[J]. Journal of Army Medical University, 2024, 46(12): 1369-1377. DOI： 10.16016/j.2097-0927.202312090.

摘要

目的

探究在氧诱导下的新生小鼠视网膜缺血模型(oxygen-induced retinopathy

OIR)中

G蛋白偶联雌激素受体(G proteincoupled estrogen receptor

GPER)减少OIR小鼠视网膜新生血管生成的机制。

方法

42只新生小鼠采用随机数字表法分为4组: 常氧对照组(

=11)、OIR组(

=11)、G-1(GPER激动剂)组(

=10)和溶剂对照组(

=10)。出生后17 d (P17)时

眼球冰冻切片免疫荧光染色观察常氧对照组小鼠GPER在视网膜分布情况。G-1组和溶剂对照组在P12~P15时分别腹腔注射给予G-1[50 μg/(kg·d)

]

或玉米油溶剂

P17时视网膜铺片免疫荧光染色观察视网膜血管标志物(IB4)、星形胶质细胞标志物胶质纤维酸性蛋白(glia fibrilary acidic protein

GFAP)表达

蛋白免疫印迹法定量检测视网膜血管内皮生长因子A (vascular endothelial growth factor A

VEGFA)、GFAP、炎症因子TNF-α、IGF-1、IL1-β蛋白表达情况。

结果

GPER存在于小鼠视网膜全层

在视网膜神经节细胞层与星形胶质细胞标志物GFAP共染。与常氧对照组相比

OIR组小鼠视网膜出现新生血管与无血管区

且GPER、VEGFA和GFAP表达增多

差异具有统计学意义(

0.05);与溶剂对照组相比

G-1组视网膜新生血管生成减少

VEGFA、GFAP、TNF-α、IGF-1、IL1-β蛋白表达下降

差异具有统计学意义(

0.05)。

结论

GPER能抑制星形胶质细胞活性

减少VEGFA、炎症因子释放

减少OIR小鼠视网膜新生血管生成。

Abstract

Objective

To investigate the mechanism by which G protein-coupled estrogen receptor (GPER) reduces retinal neovascularisation in oxygen-induced retinopathy (OIR) in newborn mice.

Methods

A total of 42 newborn mice were randomly divided into normoxic control group (

=11)

OIR group (

=11)

G-1(GPER agonist) group (

=10)

and solvent control group (

=10).On postnatal day 17(P17)

the distribution of GPER in the retina of mice in

the normoxic control group was observed by immunofluorescence staining on frozen sections of the eyeballs.The mice of the G-1 group and solvent control group were given by intraperitoneal injection 50 μg/(kg·d) G-1 or corn oil solvent from P12 to P15.Immunofluorescence staining of retinal spreads at P17 was performed to observe the expression of retinal vascular marker IB4 and astrocyte marker glia fibrilary acidic protein (GFAP).Western blotting was used to quantify the expression of retinal vascular endothelial growth factor A (VEGFA)

GFAP

and inflammatory factors TNF-α

IGF-1

and IL1-β.

Results

GPER was present throughout the retina and co-stained with the astrocyte marker GFAP in the ganglion cell layer (GCL).Compared with the normoxic control group

the retinas of mice in the OIR group showed neovascular and avascular areas

and the expression of VEGFA and GFAP was significantly increased (

0.05).Compared with the solvent control group

the retinal neovascularisation was reduced in the G-1 group

and the expression levels of VEGFA

GFAP

TNF-α

IGF-1

and IL1-β proteins were decreased significantly (

0.05).

Conclusion

GPER inhibits astrocyte activity

reduces VEGFA expression and release of inflammatory factors

and then decreases retinal neovascularisation in OIR mice.

关键词

Keywords

references

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