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08.11.2018 | Article

Prostaglandin E₂/EP₂ receptor signalling pathway promotes diabetic retinopathy in a rat model of diabetes

verfasst von: Man Wang, Yangningzhi Wang, Tianhua Xie, Pengfei Zhan, Jian Zou, Xiaowei Nie, Jun Shao, Miao Zhuang, Chengye Tan, Jianxin Tan, Youai Dai, Jie Sun, Jiantao Li, Yuehua Li, Qian Shi, Jing Leng, Xiaolu Wang, Yong Yao

Erschienen in: Diabetologia | Ausgabe 2/2019

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Abstract

Aims/hypothesis

Diabetic retinopathy is a common microvascular complication of diabetes mellitus and is initiated by inflammation and apoptosis-associated retinal endothelial cell damage. Prostaglandin E₂ (PGE₂) has emerged as a critical regulator of these biological processes. We hypothesised that modulating PGE₂ and its E-prostanoid receptor (EP₂R) would prevent diabetes mellitus-induced inflammation and microvascular dysfunction.

Methods

In a streptozotocin (STZ)-induced rat model of diabetes, rats received intravitreal injection of PGE₂, butaprost (a PGE₂/EP₂R agonist) or AH6809 (an EP₂R antagonist). Retinal histology, optical coherence tomography, ultrastructure of the retinal vascular and biochemical markers were assessed.

Results

Intravitreal injection of PGE₂ and butaprost significantly accelerated retinal vascular leakage, leucostasis and endothelial cell apoptosis in STZ-induced diabetic rats. This response was ameliorated in diabetic rats pre-treated with AH6809. In addition, pre-treatment of human retinal microvascular endothelial cells with AH6809 attenuated PGE₂- and butaprost-induced activation of caspase 1, activation of the complex containing nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like protein containing a C-terminal caspase-activation and recruitment domain (ASC), and activation of the EP₂R-coupled cAMP/protein kinase A/cAMP response element-binding protein signalling pathway.

Conclusions/interpretation

The PGE₂/EP₂R signalling pathway is involved in STZ-induced diabetic retinopathy and could be considered as a potential target for diabetic retinopathy prevention and treatment.

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Titel: Prostaglandin E2/EP2 receptor signalling pathway promotes diabetic retinopathy in a rat model of diabetes
verfasst von: Man Wang
Yangningzhi Wang
Tianhua Xie
Pengfei Zhan
Jian Zou
Xiaowei Nie
Jun Shao
Miao Zhuang
Chengye Tan
Jianxin Tan
Youai Dai
Jie Sun
Jiantao Li
Yuehua Li
Qian Shi
Jing Leng
Xiaolu Wang
Yong Yao
Publikationsdatum: 08.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 2/2019
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4755-3

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Prostaglandin E₂/EP₂ receptor signalling pathway promotes diabetic retinopathy in a rat model of diabetes

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