July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Effects of Microrna-22-3p Against Retinal Pigment Epithelial Oxidative Damage by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway.
Author Affiliations & Notes
  • Zizhong Hu
    Department of Ophthalmology, The first affiliated hospital of Nanjing Medical University, Nanjing, China
  • Ping Xie
    Department of Ophthalmology, The first affiliated hospital of Nanjing Medical University, Nanjing, China
  • Songtao Yuan
    Department of Ophthalmology, The first affiliated hospital of Nanjing Medical University, Nanjing, China
  • Qinghuai Liu
    Department of Ophthalmology, The first affiliated hospital of Nanjing Medical University, Nanjing, China
  • Footnotes
    Commercial Relationships   Zizhong Hu, None; Ping Xie, None; Songtao Yuan, None; Qinghuai Liu, None
  • Footnotes
    Support  National Key R&D Program of China. 2017YFA0104101
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1953. doi:
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      Zizhong Hu, Ping Xie, Songtao Yuan, Qinghuai Liu; Effects of Microrna-22-3p Against Retinal Pigment Epithelial Oxidative Damage by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1953.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : NLRP3, as an important inflammasome component, has crucial roles in age related macular degeneration (Nat Med. 2012 May 4;18(5):658-60.). MicroRNAs (miRNAs) have been implicated as important regulators of retinal para-inflammation. This study aimed to identify the role of microRNA-22-3p (miR-22-3p) in retinal pigment epithelial (RPE) oxidative damage by targeting NLRP3 through the inflammasome signaling pathway.

Methods : The potential miRNAs targeting NLRP3 were predicted based on TargetScan, miRDB, miRTarBase, and miRWalk databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the change of ten candidate miRNAs in retinas from albino mice after 5000 lux blue light expose. NLRP3 related protein expression was measured using qRT-PCR and Western blotting. In in-vitro studies, cell viability, ROS level, apoptosis, and NLRP3-related protein expression was measured in RPE group (Vehicle), or miRNA knockout group (KO), or miRNA mimics group (MIM), underwent lipopolysaccharide and rotenone stimulation.

Results : After light exposure, NLRP3, caspase-1, IL-1β were significantly up-regulated in mice retinas. Of 10 potential miRNAs, miRNA-22-3p was found significantly decreased. In-vitro, after 10 ug/mL LPS and 2.5 uM rotenone stimulation, ROS level were upregulated, NLRP3 inflammasome activated, and IL-1β increasingly secreted. However, we found ROS level, NLRP3 inflammasome, and IL-1β were up-regulated in miRNA-22-3p KO group while down-regulated in miRNA-22-3p MIM group.

Conclusions : Our research describes a mechanism by which miR-22-3p suppresses NLRP3 and maintains homeostasis of RPE cells and suggests miR-22-3p as a potential target for the intervention of RPE damage.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

A, In mice retinas after extensive blue light exposure, miRNA-22-3p was found significantly decreased among the 8 candidate miRNAs. B, 10 ug/mL LPS and 2.5 uM rotenone was found to be effectively induced retinal pigment epithelia cell damage. C, ROS level, NLRP3 inflammasome, and IL-1β were up-regulated in miRNA-22-3p KO group. D, ROS level, NLRP3 inflammasome, and IL-1β were down-regulated in miRNA-22-3p MIM group.

A, In mice retinas after extensive blue light exposure, miRNA-22-3p was found significantly decreased among the 8 candidate miRNAs. B, 10 ug/mL LPS and 2.5 uM rotenone was found to be effectively induced retinal pigment epithelia cell damage. C, ROS level, NLRP3 inflammasome, and IL-1β were up-regulated in miRNA-22-3p KO group. D, ROS level, NLRP3 inflammasome, and IL-1β were down-regulated in miRNA-22-3p MIM group.

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