Targeting circular RNA-ZRANB1 for therapeutic intervention in retinal neurodegeneration

Jia-Jian Wang,Rui Dong,Xiu-Miao Li,Sheng-Hai Zhang,Ji-Hong Wu,Biao Yan,Kun Shan,Chang Liu,Shu-Jie Zhang,Bai-Hui Liu,Rong-Mei Zhou

doi:10.1038/s41419-018-0597-7

Abstract

Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) loss, optic disc excavation, and progressive visual field loss. Direct or indirect ameliorating retinal neurodegeneration is a promising therapeutic therapy for glaucoma. Circular RNAs (circRNAs) are a class of covalently closed circular RNA transcripts and have emerged as potential regulators in several neurodegenerative diseases. In this study, we show that cZRANB1 expression is significantly upregulated in retinal neurodegeneration induced by glaucoma. cZRANB1 knockdown decreases retinal reactive gliosis, glial cell activation, and facilitates RGC survival in vivo. cZRANB1 knockdown directly regulates Müller cell function and indirectly regulates RGC function in vitro. cZRANB1 acts as miRNA sponge to regulate Müller cell function through cZRANB1/miR-217/RUNX2 network. Intervention of cZRANB1 expression would become an effective strategy for treating retinal neurodegeneration.

Highlights

Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) loss, optic disc excavation, and progressive visual field loss
We reveal that cZRANB1 expression is significantly upregulated in the glaucomatous retinas. cZRANB1 knockdown significantly decreases retinal reactive gliosis, inhibits Müller cell activation, and facilitates RGC survival. cZRANB1 knockdown directly regulates Müller cell function but indirectly regulates RGC function in vitro
Glaucoma is a leading cause of irreversible vision loss characterized by retinal neurodegeneration, including progressive RGC loss and axon degeneration

Summary

Introduction

Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) loss, optic disc excavation, and progressive visual field loss. We show that cZRANB1 expression is significantly upregulated in retinal neurodegeneration induced by glaucoma. 1234567890():,; 1234567890():,; Glaucoma is recognized as a retinal neurodegenerative disease characterized by retinal ganglion cell (RGC) loss, optic disc excavation, and progressive visual field loss[1]. It is a major cause of vision impairment and irreversible blindness in the world[2]. CZRANB1 knockdown significantly decreases retinal reactive gliosis, inhibits Müller cell activation, and facilitates RGC survival. Intervention of cZRANB1 expression would become a promising therapeutic strategy for retinal neurodegeneration

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Conclusion