Open AccessThe G‐protein‐coupled chemoattractant receptor Fpr2 exacerbates neuroglial dysfunction and angiogenesis in diabetic retinopathy
Author(s) -
Yu Ying,
Xue Shengding,
Chen Keqiang,
Le Yingying,
Zhu Rongrong,
Wang Shiyi,
Liu Shuang,
Cheng Xinliang,
Guan Huaijin,
Wang Ji Ming,
Chen Hui
Publication year - 2020
Publication title -
faseb bioadvances
Language(s) - English
Resource type - Journals
ISSN - 2573-9832
DOI - 10.1096/fba.2020-00034
Subject(s) - diabetic retinopathy , angiogenesis , retina , neovascularization , retinal , downregulation and upregulation , retinopathy , microglia , medicine , proinflammatory cytokine , cancer research , receptor , immunology , inflammation , biology , endocrinology , diabetes mellitus , neuroscience , ophthalmology , biochemistry , gene
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 Fpr2 −/− 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.