2. Academic Validation
  3. Prostaglandin E2 promotes pathological retinal neovascularisation via EP4R-EGFR-Gab1-AKT signaling pathway

Prostaglandin E2 promotes pathological retinal neovascularisation via EP4R-EGFR-Gab1-AKT signaling pathway

  • Exp Eye Res. 2021 Apr;205:108507. doi: 10.1016/j.exer.2021.108507.
Tianhua Xie 1,  Zhonghong Zhang 2,  Yuqing Cui 3,  Yishun Shu 3,  Yanqiu Liu 3,  Jian Zou 4,  Man Wang 3,  Yangningzhi Wang 3,  Qian Yang 5,  Xubin Pan 6,  Jiping Cai 3,  Xiaodong Sun 7,  Yong Yao 8,  Xiaolu Wang 9
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, PR China.
  • 2 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Department of Ophthalmology, Zhongda Hospital Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu, 210009, PR China.
  • 3 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China.
  • 4 Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China.
  • 5 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China.
  • 6 Department of Ophthalmology, Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, Jiangsu, 214062, PR China.
  • 7 Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, PR China.
  • 8 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China. Electronic address: yongyao@njmu.edu.cn.
  • 9 Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China. Electronic address: xlwang@njmu.edu.cn.
PMID: 33609510 DOI: 10.1016/j.exer.2021.108507
Abstract

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E2 (PGE2) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP4R). The aim of this study was to investigate the role of PGE2/EP4R signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE2, cay10598 (an EP4R agonist) or AH23848 (an EP4R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE2 or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE2-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE2 or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE2-or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE2/EP4R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.

Keywords

EGF receptor; EP(4)R; Endothelial cell; PGE(2); Retinal angiogenesis.

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