MicroRNA‐141‐3p inhibits retinal neovascularization and retinal ganglion cell apoptosis in glaucoma mice through the inactivation of Docking protein 5‐dependent mitogen‐activated protein kinase signaling pathway

Abstract

Retinal neovascularization occurs in various ocular disorders including proliferative diabetic retinopathy and secondary neovascular glaucoma, resulting in blindness. This paper aims to investigate the effect of microRNA‐141‐3p (miR‐141‐3p) on retinal neovascularization and retinal ganglion cells (RGCs) in glaucoma mice through the Docking protein 5 (DOK5)‐mediated mitogen‐activated protein kinase (MAPK) signaling pathway. Chip retrieval and difference analysis were used for the potential mechanism of miR‐141‐3p on glaucoma. All modeled mice were transfected with different expression of mimic or inhibitor. The expressions of miR‐141‐3p, DOK5, and related genes and proteins of the MAPK signaling pathway were detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. Cell proliferation, lumen formation, and apoptosis in the retinal vascular epithelial cells and RGCs were detected using Matrigel angiogenesis and terminal deoxynucleotidyl transferase mediated dUTP nick‐end labeling assays. Moreover, a total of 63 and 294 differentially expressed genes were obtained in GSE2378 and GSE9944 chips, and 4 genes were within the intersection of the chips. In addition, the results showed that miR‐141‐3p was found to inhibit the DOK5 gene and activate the MAPK pathway. The number of RGCs, the expression of p38, extracellular‐signal‐regulated kinases (ERK), Jun N‐terminal kinase (JNK), IGF‐1, VEGF, HIF1‐α, Bax, caspase‐3, and the extent of p38, ERK, and JNK phosphorylated were decreased with miR‐141‐3p upregulation. Lastly, the results obtained showed that miR‐141‐3p inhibited the proliferation of retinal vascular epithelial cells and inhibited angiogenesis, as well as promoted apoptosis of RGCs. The study suggests that miR‐141‐3p inhibits retinal neovascularization in glaucoma mice by impeding the activation of the DOK5‐mediated MAPK signaling pathway.

miR-590-3pInhibits Pyroptosis in Diabetic Retinopathy by TargetingNLRP1and Inactivating the NOX4 Signaling Pathway

“…24 In our study, we found that the activity and expression of caspase-1 and IL-1b were significantly increased in HG-treated HRMECs and clinical vitreous samples, suggesting that pyroptosis is involved in the pathogenesis of DR. Increasing evidence has demonstrated that miRNAs function as effective biomarkers or therapeutic targets, 25 and many miRNAs have been shown to have important roles in DR progression. 26,27 In our study, we initially investigated the role in DR of miR-590-3p, which is an inflammation-related miRNA 16,18,28 that may participate in the progression of pyroptosis. Our results indicated that the miR-590-3p inhibitor induced pyroptosis, which is consistent with the HG-induced condition.…”

Viral delivery of multiple miRNAs promotes retinal ganglion cell survival and functional preservation after optic nerve crush injury

“…A recent experiment utilized 12-week DBA/2J mice that received an injection of glutamate to induce RGC excitotoxicity. Intravitreal delivery of a virus expressing miR-141-3p led to a significant increase in RGC survival along with downregulation of apoptotic signalling pathways such as Bax and caspase-3 (Zhang et al, 2018).…”

Proteomics Reveals the Potential Protective Mechanism of Hydrogen Sulfide on Retinal Ganglion Cells in an Ischemia/Reperfusion Injury Animal Model

“…Slc2a1 abundance in HIF1α signaling plays a key role in promoting neuronal survival by mediating the endogenous protective responses after hypoxia-ischemia. In glaucoma mice, decreased HIF1α expression is observed to be correlated with RGC loss [ 56 ]. H 2 S regulates HIF1 factors in different patterns, depending on different cell types and experimental conditions.…”