增生性视网膜病变，例如增生性糖尿病视网膜病变（PDR）和早产儿视网膜病变（ROP），是工业化国家视力障碍和失明的主要原因。前列腺素E
2
（PGE
2
）通过E-前列腺素受体（EP
4
R）参与细胞增殖和迁移。这项研究的目的是调查PGE
2
/ EP
4
R信号在促进视网膜新血管形成中的作用。在链脲佐菌素（STZ）诱导的糖尿病模型和氧诱导性视网膜病变（OIR）模型中，大鼠接受玻璃体内注射PGE
2
，cay10598（EP
4
R激动剂）或AH23848（EP
4
R拮抗剂）。光学相干断层扫描，视网膜组织学和生化标记进行了评估。用PGE
2
或cay10598处理可加速STZ和OIR诱导的大鼠视网膜的病理性视网膜血管生成，在用AH23848预处理的大鼠中可改善这种情况。与未治疗的糖尿病大鼠相比，在PGE
2
治疗的糖尿病大鼠中血清VEGF-A被上调，而在AH23848治疗的糖尿病大鼠中血清VEGF-A被显着下调。PGE
2
或cay10598处理还可以显着促进新生大鼠视网膜中内皮尖端细胞的形成。此外，AH23848处理可减弱PGE
2
-或cay10598诱导的增殖和迁移通过抑制人视网膜微血管内皮细胞中的EGF受体（EGFR）/生长因子受体结合蛋白2相关结合蛋白1（Gab1）/ Akt /NF-κB/ VEGF-A信号网络hRMEC）。因此，PGE
2
/ EP
4
R信号网络是病理性眼内血管生成的潜在治疗靶标。
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 E
2
(PGE
2
) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP
4
R). The aim of this study was to investigate the role of PGE
2
/EP
4
R 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 PGE
2
, cay10598 (an EP
4
R agonist) or AH23848 (an EP
4
R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE
2
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 PGE
2
-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE
2
or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE
2
-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). PGE
2
/EP
4
R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.
