Effects of miR-21/NLRP3 on Blue Light-Induced Retinal Neurodegeneration in Mice.

Abstract

Purpose: Age-related macular degeneration (AMD) is a chronic retinal disease that can lead to blindness. While the NLR family pyrin domain containing 3 (NLRP3) inflammasome is implicated in AMD, the specific roles of miR-21 and NLRP3 in AMD-related inflammation remain unclear. Therefore, this study aimed to investigate the roles of miR-21 and NLRP3 in blue light-induced neurodegeneration in the mouse retina.

Methods: A mouse model of retinal light damage was established through three months of blue light exposure (BLE). The experimental groups comprised the Control (Ctrl), BLE, BLE + miR-nc, and BLE + miR-21 inhibitor groups. The microRNAs were administered via intravitreal injections once per week. After successful modeling, changes in visual function and retinal morphology were investigated by using electroretinography and hematoxylin and eosin staining, respectively. Photoreceptor apoptosis was assessed using the TdT-mediated dUTP nick-end labeling assay. Immunofluorescence was used to detect and locate microglia and NLRP3 expression in the mouse retina. The expression of miR-21, NLRP3, and downstream factors in the retinas of each group was measured using qRT-PCR and western blotting.

Results: In the BLE and BLE + miR-nc groups, there was a decrease in visual function and retinal thickness, an increase in retinal ganglion cell injury and photoreceptor cell apoptosis, and elevated microglia activity in the retina, as evidenced by their migration to the outer retinal layer. In addition, the expression of miR-21, NLRP3, and downstream factors was increased in the BLE and BLE + miR-nc groups compared to that in the control group. However, intravitreal injection of the miR-21 inhibitor reduced miR-21 expression in the retina and significantly inhibited the activation of the NLRP3 inflammasome, effectively alleviating retinal photodamage caused by BLE.

Conclusions: This study indicates that miR-21 may mitigate blue-light-induced retinal neurodegeneration by reducing the activation of the NLRP3 inflammasome in the mouse retina.