Yu Ying, Xue Shengding, Chen Keqiang, Le Yingying, Zhu Rongrong, Wang Shiyi, Liu Shuang, Cheng Xinliang, Guan Huaijin, Wang Ji Ming, Chen Hui
Eye Institute Affiliated Hospital of Nantong University Nantong China.
Cancer and Inflammation Program Center for Cancer Research National Cancer Institute at Frederick Frederick MD USA.
FASEB Bioadv. 2020 Sep 15;2(10):613-623. doi: 10.1096/fba.2020-00034. eCollection 2020 Oct.
Diabetic retinopathy (DR) as a retinal neovascularization-related disease is one of the leading causes of irreversible blindness in patients. The goal of this study is to determine the role of a G-protein-coupled chemoattractant receptor (GPCR) FPR2 (mouse Fpr2) in the progression of DR, in order to identify novel therapeutic targets. We report that Fpr2 was markedly upregulated in mouse diabetic retinas, especially in retinal vascular endothelial cells, in associated with increased number of activated microglia and Müller glial cells. In contrast, in the retina of diabetic mice, the activation of vascular endothelial cells and glia was attenuated with reduced production of proinflammatory cytokines. Fpr2 deficiency also prevented the formation of acellular capillary during diabetic progression. Furthermore, in oxygen-induced retinopathy (OIR) mice, the absence of Fpr2 was associated with diminished neovasculature formation and pathological vaso-obliteration region in the retina. These results highlight the importance of Fpr2 in exacerbating the progression of neuroglial degeneration and angiogenesis in DR and its potential as a therapeutic target.
糖尿病性视网膜病变（DR）作为一种与视网膜新生血管形成相关的疾病，是导致患者不可逆失明的主要原因之一。本研究的目的是确定G蛋白偶联趋化因子受体（GPCR）FPR2（小鼠Fpr2）在DR进展中的作用，以识别新的治疗靶点。我们报告，Fpr2在小鼠糖尿病视网膜中显著上调，尤其是在视网膜血管内皮细胞中，这与活化的小胶质细胞和Müller胶质细胞数量增加有关。相反，在糖尿病小鼠的视网膜中，血管内皮细胞和胶质细胞的活化减弱，促炎细胞因子的产生减少。Fpr2缺乏也可防止糖尿病进展过程中无细胞毛细血管的形成。此外，在氧诱导性视网膜病变（OIR）小鼠中，Fpr2的缺失与视网膜新生血管形成减少和病理性血管闭塞区域减少有关。这些结果突出了Fpr2在加剧DR中神经胶质细胞变性和血管生成进展中的重要性及其作为治疗靶点的潜力。
