Received: 12 February 2019 | Accepted: 25 February 2019 DOI: 10.1002/jcp.28523 ORIGINAL RESEARCH ARTICLE Protective effects of microRNA‐22‐3p against retinal pigment epithelial inflammatory damage by targeting NLRP3 inflammasome Zizhong Hu 1 * | Xuehua Lv 1,2 * | Lu Chen 1 | Xunyi Gu 1 | Huiming Qian 1 | Silvia Fransisca 1 | Zhengyu Zhang 1 | Qinghuai Liu 1 | Ping Xie 1 1 Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 2 Department of Ophthalmology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Correspondence Prof. Qinghuai Liu and Prof. Ping Xie, 300 Guangzhou Road, Nanjing, 210029 Jiangsu, China. Email: liuqh@njmu.edu.cn (QL); xieping9@126.com (PX) Funding information General Project of the National Natural Science, Grant/Award Number: 81870669; Key Project of Research and Development Plan, Grant/Award Number: 2017YFA0104101; General Project of Jiangsu Natural Science, Grant/Award Number: BK20171503 Abstract NLRP3, as a crucial inflammasome component, plays important roles in age‐related macular degeneration. Though some activators of NLRP3 have been studied, microRNAs (miRNAs) which potentially regulate NLRP3 messenger RNA (mRNA) have not been fully explored in retinal pigment epithelial (RPE) cells and retinopathy. In this study, by miRNA microarray profiling and bioinformatic analysis, we identified that four miRNAs, miR‐4286, miR‐223‐3p, miR‐365a, miR‐22‐3p, may target NLRP3 mRNA in RPE inflammatory damage in vivo. Further, real‐time polymerase chain reaction verified that only miR‐22‐3p was significantly decreased, which was associated with NLRP3 upregulation in blue‐light‐induced retinopathy. Mechanistically, the dual‐fluorescent reporter suggested miR‐22‐3p directly binds NLRP3 mRNA. Moreover, overexpression of miR‐22‐3p could significantly reduce whereas inhibition miR‐22‐3p could increase the mRNA and protein expressions of NLRP3, Caspase‐1, and mature IL‐1β. Collectively, our results indicate that miR‐22‐3p plays a suppressive role in RPE damage by targeting NLRP3, which provides new insights into the future intervention to retinopathy. KEYWORDS miR‐22‐3p, NLRP3, retinal pigment epithelia, retinopathy 1 | INTRODUCTION Age‐related macular degeneration (AMD), the primary cause of vision loss and even blindness in elderly population, can deteriorate the quality of life and increase the economic burden. AMD has both wet and dry forms (Lim, Mitchell, Seddon, Holz, & Wong, 2012). Wet AMD is featured as choroidal neovasculariza- tion (CNV), involving abnormal neovascularization from the choroid. During the past two decades, vascular endothelial growth factor (VEGF) has been acknowledged as the crucial regulator promoting the growth of immature and leaky vessels, leading to loss of vision (Miller, Le Couter, Strauss, & Ferrara, 2013). Recently, anti‐VEGF therapy has been demonstrated successful on the treatment of wet‐AMD (Villegas, Aranguren, Kovach, Schwartz, & Flynn, 2017). As for dry AMD, which manifests by scattered or degenerated areas of retinal pigment epithelial (RPE) cells, so far has no effective therapy. Thus, it is of great significance to explore the mechanism of AMD pathogenesis and to develop effective therapeutic strategies to stop its progression. The geographic atrophy in dry AMD is initiated by the degeneration of RPE cells, and later the photoreceptor cells. A normally functioning RPE is indispensable for vision, whereas the impaired function of RPE is thought as the major factor responsible J Cell Physiol. 2019;1–9. wileyonlinelibrary.com/journal/jcp © 2019 Wiley Periodicals, Inc. | 1 *Hu and Lv have contributed equally to this study.