Silencing of circular RNA‑ZYG11B exerts a neuroprotective effect against retinal neurodegeneration

Abstract

Ischemic retinal diseases are the major cause of vision impairment worldwide. Currently, there are no available treatments for ischemia-induced retinal neurodegeneration. Circular RNAs (circRNAs) have emerged as important regulators of several biological processes and human diseases. The present study investigated the role of circRNA-ZYG11B (circ-ZYG11B; hsa_circ_0003739) in retinal neurodegeneration. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) demonstrated that circZYG11B expression was markedly increased during retinal neurodegeneration in vivo and in vitro . Cell Counting Kit-8, TUNEL and caspase-3 activity assays revealed that silencing of circZYG11B was able to protect against oxidative stress- or hypoxic stress-induced retinal ganglion cell (RGC) injury. Furthermore, immunofluorescence staining and hematoxylin and eosin staining revealed that silencing of circZYG11B alleviated ischemia/reperfusion-induced retinal neurodegeneration, as indicated by reduced RGC injury and decreased retinal reactive gliosis. In addition, luciferase reporter, biotin-coupled miRNA capture and RNA immunoprecipitation assays revealed that circZYG11B could regulate RGC function through circZYG11B/microRNA-620/PTEN signaling. Clinically, RT-qPCR assays demonstrated that circZYG11B expression was markedly increased in the aqueous humor of patients with glaucoma. In conclusion, circZYG11B may be considered a promising target for the diagnosis and treatment of retinal ischemic diseases.

Targeting circular RNA-Glra2 alleviates retinal neurodegeneration induced by ocular hypertension

“…cZRANB1 expression is significantly up-regulated during retinal neurodegeneration. Targeting cZRANB1 is an effective strategy for treating retinal neurodegeneration [ 2 , 11 , 12 ]. In this study, we reveal that silencing of cGlra2 can alleviate RGC apoptosis, decrease reactive gliosis, and reduce retinal cell apoptosis.…”

“…We thus speculated that circRNAs also played critical roles in the process of retinal neurodegeneration. Previous studies have revealed that silencing of circZYG11B, circZNF609, or circZRANB1 plays a neuroprotective role in retinal neurodegeneration [ 11 , 12 ]. A study has been conducted to identify glaucoma-related cicRNAs in a rat glaucomatous model [ 13 ].…”

The Application of MicroRNAs in Glaucoma Research: A Bibliometric and Visualized Analysis

“…The sponging of miRNAs by circRNAs in most disorders highlights their potential as therapy candidates or biomarkers. For example, silencing circZYG11B could suppress I/R-induced RGC injury and attenuate I/R-induced retinal reactive gliosis through circZYG11B/microRNA-620/PTEN signaling; thus, circZYG11B might be a candidate for the identification and therapy of retinal ischemic diseases [135]. Chen et al [136] revealed that circHipk2 and circTulp4 can serve as sponges of miR-124-3p and miR-204-5p/miR-26a-5p, respectively, and the interruption of circTulp4 expression induced impaired retinal function.…”

Retinal neurodegeneration in metabolic syndrome: a spectral optical coherence tomography study

“…Several studies confirmed that RNFL and GCL thickness reduction precede functional deficits [8][9] . There is no proven treatment for retinal neurodegeneration but ongoing studies are aiming to provide evidence for treatment and neuroprotection [10][11] . There are many studies on the effects of MetS criteria such as HT, diabetes mellitus (DM), VO, and dyslipidemia on the retina [3,[12][13][14] .…”