Circular Rims2 Deficiency Causes Retinal Degeneration. Issue 12 (5th November 2021)

• Record Type: Journal Article
• Authors: Sun, Lan‐Fang; Ma, Yue; Ji, Yang‐Yang; Wu, Zhen; Wang, Ya‐Han; Mou, Hao; Jin, Zi‐Bing
• Is Part Of: Advanced biology. Volume 5:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-05
• Subjects: circRims2 -- circRNA -- retinal degeneration -- TNF signaling pathway; Molecular biology -- Periodicals; Systems biology -- Periodicals; Biological systems -- Periodicals; Biotechnology -- Periodicals; Bioengineering -- Periodicals; Biomedical engineering -- Periodicals; 660.6
• DOI: 10.1002/adbi.202100906
• Languages: English
• ISSNs: 2701-0198

Abstract

Abstract: Circular RNAs (circRNAs) refer to a newly recognized family of non‐coding RNA with single‐stranded RNAs. Despite emerging evidence indicating that circRNAs are abundantly expressed in various tissues, especially in the brain and retina, the role of circRNAs in retinal function and diseases is still largely unknown. Circular Rims2 (circRims2) is highly expressed and conserved in both the human and mouse brains. However, little is known about the expression and function of circRims2 in the retina. In the current study, the high‐throughput RNA‐seq analysis reveals a high expression of circRims2 in the retina. In addition, it is found that circRims2 is mainly located in plexiform layers that contain synapses between retinal neurons. Knocking down circRims2 with short hairpin RNA through subretinal adeno‐associated viral (AAV) delivery in the mice leads to the decrease of the thickness of the outer and inner segment (OS/IS) layers and outer nuclear layer (ONL), and cessation of scotopic and photopic electroretinogram responses. Furthermore, the current study finds that circRims2 deficiency evokes retinal inflammation and activates the tumor necrosis factor (TNF) signaling pathway. Therefore, circRims2 may play an important role in the maintenance of retinal structure and function, and circRims2 deficiency may lead to pathogenic changes in the retina. Abstract : In this study, a circular RNA, circRims2, is discovered, which is crucial for retinal maintenance and function. Targeted silence of circRims2, but not linear Rims2, leads to significant damages of neurons in the retina. Furthermore, the retinal cell apoptosis is mediated by the tumor necrosis factor (TNF) signaling pathway.