Brain-derived neurotrophic factor is a novel target gene of the hsa-miR-183/96/182 cluster in retinal pigment epithelial cells following visible light exposure

Abstract

Light-induced retinal injury is clinically and experimentally well-documented. It may be categorized into three types: Photothermal, photomechanical and photochemical injuries. To date, the variation in the hsa-miR-183/96/182 cluster and its potential target genes in human primary retinal pigment epithelial (RPE) cells, following visible light exposure, has not been reported. In the present study, RPE cells were exposed to 4 h of constant visible light. The expression of the hsa-miR-183/96/182 cluster was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and its potential target genes were investigated. Additionally, hsa-miR-183, hsa-miR-96, hsa-miR-182 and has-miR-183/96/182 mimics were designed and synthesized in vitro, and transfected into the RPE cells. Subsequently, the expression of brain-derived neurotrophic factor (BDNF) mRNA and protein was measured, using RT-qPCR and western blotting, respectively. The regulation of miRNAs to the BDNF gene were then validated using a dual luciferase reporter gene assay system. The expression of hsa-miR-183, hsa-miR-96 and hsa-miR-182 significantly increased in RPE cells following 4 h of visible light exposure, compared with RPE cells that had been exposed to dark conditions (P<0.01). Following RPE cell transfection with mimics, BDNF mRNA and protein expression in the RPE cells was significantly downregulated compared with control RPE cells (P<0.05, P<0.01, respectively). Similarly, the ratio of Renilla luciferase/firefly luciferase significantly decreased in the RPE cells of the mimic + wild type (WT) group compared with cells of the psiCHECK(TM)-2 (a vector lacking the sequence of the BDNF gene), wild type and mimic + mutation groups (P<0.05, P<0.01). The present study suggests that BDNF is a target gene of the has-miR-183-96-182 cluster in RPE cells. The present study suggests an underlying protective mechanism against retinal light injury and may provide a novel target for the prevention and treatment of light-induced retinal injury.

Resource: A multi‐species multi‐timepoint transcriptome database and webpage for the pineal gland and retina

“…Accordingly, it can be considered to be an additional marker of the common ancestral photodetector which gave rise to the pineal gland and retina. Although the function of this cluster remains unknown in the pineal gland, it has been reported to play a role in phototransduction and development in the eye 30,31 …”

Growth of malignant extracranial tumors alters microRNAome in the prefrontal cortex of TumorGraft mice

“…BDNF is a member of the nerve growth factor family and one of the fundamental factors regulating neuronal growth, maturation and survival in the brain and spinal cord [ 52 ]. Among the other miRNAs, the miR-183/96/182 family and miR-10b target BDNF as well [ 51 , 53 ]. With this in mind, using western immunoblotting, we analyzed the levels of BDNF in the PFC tissues of intact controls, and TNBC and PR+BC tumor-bearing treated and untreated mice.…”

“…The miR-183/96/182 cluster upregulated in the PR+BC tumor-bearing treated and untreated mice was implicated in hepatocellular carcinoma, breast cancer, and glioma [ 85 - 87 ]. It has also been linked with light-induced retinal injury and was shown to target brain-derived neurotrophic factor (BDNF) [ 53 ]. BDNF is also a target of miR-191 that was upregulated in all experimental animal groups, as compared to controls [ 51 ].…”

LncRNA Riken‐201 and Riken‐203 modulates neural development by regulating the Sox6 through sequestering miRNAs

“…53 miR-96 is also reported to target important nerve growth factor family member BDNF 54,55 that is also involved in the increasing survival of photoreceptors in retinal pigment epithelial (RPE) cells. 56 Sevoflurane, the most commonly used general anaesthetic in children, induces neurotoxicity and cognitive impairment in young mice 35 and inhibits neurogenesis in vitro. 60,61 The mechanisms by which these effects are created have yet to be identified, impeding further research in anaesthesia neurotoxicity in the developing brain.…”