Chen Tingting, Wang Congyao, Zhu Wenhui, Yu Fenfen, Dong Xia, Su Yihua, Huang Jingwen, Huo Lijun, Wan Pengxia
Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
Cell Signal. 2024 May;117:111121. doi: 10.1016/j.cellsig.2024.111121. Epub 2024 Feb 27.
Diabetic retinopathy (DR) is still the major cause of visual loss in working-aged people, one of the critical pathological processes are retinal microglia-mediated inflammation. Our previous study demonstrated that enhanced M1 microglial polarization was involved in retinal inflammation in DR, but the detailed mechanism needs further investigation. Circular RNAs (circRNAs) are important kind of noncoding RNAs involved in the regulation of various cell biological processes. Herein, the circRNA expression profiles of BV2 mouse microglia treated with or without glucose were detected, and a total of 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells. The key circRNA mm9_circ_014683 increased after glucose stimulation. Inhibiting or overexpressing mm9_circ_014683 showed no effect on the proliferation and apoptosis of microglia. Inhibiting mm9_circ_014683 impeded M1 polarization and promoted M2 polarization, and overexpressing mm9_circ_014683 showed the opposite effect. A total of 216 differentially expressed genes were identified in mm9_circ_014683-knockdown BV2 cells, which were enriched in several signaling pathways, including the NFκB signaling pathway. Moreover, mm9_circ_014683 positively regulated the canonical, NFκB signaling pathway. Besides, mm9_circ_014683 was highly expressed in the retinal microglia of diabetic mice, and intraocular injection of Lv-circRNA inhibited M1 but enhanced M2 retinal microglial polarization. In conclusion, mm9_circ_014683 regulates microglial polarization through the canonical NFκB signaling pathway in diabetic retinopathy. This study may provide insight into the pathogenesis and treatment of DR.
糖尿病视网膜病变（DR）仍是劳动年龄人群视力丧失的主要原因，关键的病理过程之一是视网膜小胶质细胞介导的炎症。我们之前的研究表明，增强的M1小胶质细胞极化参与了DR中的视网膜炎症，但具体机制仍需进一步研究。环状RNA（circRNAs）是一类重要的非编码RNA，参与多种细胞生物学过程的调控。在此，我们检测了用葡萄糖处理或未处理的BV2小鼠小胶质细胞的circRNA表达谱，在葡萄糖处理的BV2细胞中总共鉴定出347个差异表达的circRNAs。关键的circRNA mm9_circ_014683在葡萄糖刺激后增加。抑制或过表达mm9_circ_014683对小胶质细胞的增殖和凋亡没有影响。抑制mm9_circ_014683可阻碍M1极化并促进M2极化，而过表达mm9_circ_014683则显示出相反的效果。在mm9_circ_014683敲低的BV2细胞中总共鉴定出216个差异表达基因，这些基因富集于包括NFκB信号通路在内的几种信号通路中。此外，mm9_circ_014683正向调节经典的NFκB信号通路。此外，mm9_circ_014683在糖尿病小鼠的视网膜小胶质细胞中高表达，眼内注射Lv-circRNA可抑制M1但增强M2视网膜小胶质细胞极化。总之，mm9_circ_014683在糖尿病视网膜病变中通过经典的NFκB信号通路调节小胶质细胞极化。本研究可能为DR的发病机制和治疗提供见解。
