Targeting circular RNA-ZRANB1 for therapeutic intervention in retinal neurodegeneration

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 Muller cell function and indirectly regulates RGC function in vitro. cZRANBI acts as miRNA sponge to regulate Muller cell function through cZRANB1/miR-217/RUNX2 network Intervention of cZRANBI expression would become an effective strategy for treating retinal neurodegeneration.